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BIOMARKER:

ATRX mutation

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Other names: ATRX, ATRX Chromatin Remodeler, Transcriptional Regulator ATRX, ATP-Dependent Helicase ATRX, X-Linked Nuclear Protein, X-Linked Helicase II, XH2, XNP, Alpha Thalassemia/Mental Retardation Syndrome X-Linked (RAD54 (S. Cerevisiae) Homolog), Alpha Thalassemia/Mental Retardation Syndrome X-Linked (RAD54 Homolog S. Cerevisiae), Alpha Thalassemia/Mental Retardation Syndrome X-Linked, Mental Retardation X-Linked 52, RAD54 Homolog (S. Cerevisiae), Juberg-Marsidi Syndrome, ZNF-HX, Znf-HX, MRX52, JMS
Entrez ID:
Related biomarkers:
8d
Utility of Targeted Next-Generation Sequencing Assay to Detect 1p/19q Co-Deletion in Formalin-fixed Paraffin-embedded Glioma Specimens. (PubMed, Hum Pathol)
The oligodendroglioma cohort had more mutations in IDH1/IDH2, CIC, FUBP1, and TERT, and fewer mutations in ATRX and TP53 than the non-oligodendroglioma cohort. This proof-of-concept study demonstrated that targeted NGS can simultaneously detect both 1p/19q co-deletion and somatic mutations, which can provide a more comprehensive genetic profiling for patients with gliomas using a single assay in a clinical setting.
Journal • Next-generation sequencing
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • IDH1 mutation • IDH2 mutation • ATRX mutation • TERT mutation • IDH wild-type
19d
ATRX-dependent SVCT2 mediates macrophage infiltration in the glioblastoma xenograft model. (PubMed, J Neurophysiol)
siRNA interference of ATRX-dependent SVCT2 signal with shSVCT2 could inhibit tumor cell proliferation in Glu261-LuNeo xenograft tumor model with more survival advantage, probably by the inhibited macrophage chemotaxis. These results indicate that ATRX-dependent SVCT2-mediated chemokine-induced macrophage infiltration is regulated by the NF-κB pathway, which could be considered as treatment targets.
Preclinical • Journal
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ATRX (ATRX Chromatin Remodeler) • CCL2 (Chemokine (C-C motif) ligand 2) • CXCL5 (Chemokine (C-X-C motif) ligand 5) • NFKBIA (NFKB Inhibitor Alpha 2) • JUN (Jun proto-oncogene) • CXCL1 (Chemokine (C-X-C motif) ligand 1)
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ATRX mutation • CXCL8 expression
24d
A nomogram strategy for identifying the subclassification of IDH mutation and ATRX expression loss in lower-grade gliomas. (PubMed, Eur Radiol)
• Non-invasive determination of IDH and ATRX gene status of LrGG patients can be obtained with a radiomics nomogram. • The proposed nomogram is constructed by radiomics signature selected from 250 radiomics features, combined with age and gender. • The proposed radiomics nomogram exhibited good calibration and discrimination for IDH and ATRX gene mutation stratification of LrGG patients in both training and validation sets.
Retrospective data • Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
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IDH1 mutation • ATRX mutation • IDH wild-type
25d
Vaginal melanoma in Denmark from 1980 to 2018: A population-based study based on genetic profile and survival. (PubMed, Gynecol Oncol)
Vaginal melanoma is a rare disease with a poor prognosis presumably due to vague symptoms and the anatomical location of the disease. Co-mutations in ATRX and TP53 and mutations in TP53 alone were associated with a poor prognosis, and these genes are potentially interesting targets for future therapy.
Journal
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TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation
1m
MUTATIONAL LANDSCAPE OF ALTERNATIVE LENGTHENING OF TELOMERES IN PEDIATRIC BRAIN CANCER (ASPHO 2022)
We demonstrate that ATRX is only mutated in 58% of ALT+ HGAT, suggesting that other means of ATRX loss of function or other mutations may be associated with the development of ALT in these patients. Additionally, we show that germline variants in MMR genes are associated with an increased rate of ALT+ tumors, suggesting that loss of MMR function may result in a permissive state that promotes the development of ALT. Future studies will focus on elucidating the relationship between MMR function and ALT development, as well as identifying other mutations that drive the maintenance and development of ALT.
Clinical
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TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation
1m
ATRX-Deficient High-Grade Glioma Cells Exhibit Increased Sensitivity to RTK and PDGFR Inhibitors. (PubMed, Cancers (Basel))
Furthermore, we demonstrate that a combinatorial treatment of RTKi with temozolomide (TMZ)-the current standard of care treatment for GBM patients-causes pronounced toxicity in ATRX-deficient high-grade glioma cells. Our findings suggest that combinatorial treatments with TMZ and RTKi may increase the therapeutic window of opportunity in patients who suffer high-grade gliomas with ATRX mutations. Thus, we recommend incorporating the ATRX status into the analyses of clinical trials with RTKi and PDGFRi.
Journal
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ATRX (ATRX Chromatin Remodeler) • SMARCA2 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily A, Member 2)
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ATRX mutation
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temozolomide
1m
Upfront Molecular Targeted Therapy for the Treatment of BRAF-Mutant Pediatric High-Grade Glioma. (PubMed, Neuro Oncol)
Upfront targeted therapy for patients with BRAF-mutant pHGG is feasible and effective, with superior clinical outcomes compared to historical data. This promising treatment paradigm is currently being evaluated prospectively in the Children's Oncology Group ACNS1723 clinical trial.
Journal
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)
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EGFR mutation • BRAF mutation • ATRX mutation
1m
Review • Journal
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler)
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PTEN mutation • NF1 mutation • ATRX mutation
1m
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=30, Completed, Massachusetts General Hospital | Active, not recruiting --> Completed
Trial completion
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
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BRCA2 mutation • BRCA1 mutation • ATM mutation • MYC amplification • ARID1A mutation • CDK12 mutation • CCNE1 amplification • ATRX mutation • FBXW7 mutation • BRIP1 mutation • CHEK2 mutation • FANCA mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
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OncoPanel™ Assay
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berzosertib (M6620)
2ms
Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor. (PubMed, Sci Rep)
Functional and biochemical studies demonstrated these PNKP mutations significantly diminished DNA kinase/phosphatase activities, altered its cellular distribution, caused defective repair of DNA single/double stranded breaks, and were associated with a higher propensity for oncogenic transformation. Our findings indicate that specific PNKP mutations may contribute to tumor initiation within susceptible cells in the CNS by limiting DNA damage repair and increasing rates of spontaneous mutations resulting in pediatric glioma associated driver mutations such as ATRX and TP53.
Journal
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TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation
2ms
The mutational spectrum of ATRX aberrations in neuroblastoma and the associated patient and tumor characteristics. (PubMed, Cancer Sci)
Surprisingly, we found that 11q deletions are enriched in neuroblastomas with ATRX deletions compared to a reference cohort, but not in neuroblastomas with ATRX point mutations. Taken together our data emphasizes a distinct ATRX mutation spectrum in neuroblastoma, which should be considered when studying molecular phenotypes and therapeutic strategies.
Journal
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ATRX (ATRX Chromatin Remodeler)
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Chr del(11q) • ATRX mutation • ATRX deletion
2ms
Choroidal melanoma with synchronous Fuchs' adenoma and novel ATRX mutation. (PubMed, Int J Retina Vitreous)
Fuchs' adenoma is an under-diagnosed benign age-related hyperplasia of the non-pigmented ciliary epithelium (NPCE). Given its location and characteristics, it can be mistaken for choroidal melanoma and clinicians are reminded how to differentiate between these pathologies and that they may co-exist.
Journal
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
2ms
Molecular landscape of pediatric type IDH wildtype, H3 wildtype hemispheric glioblastomas. (PubMed, Lab Invest)
Of the other common biomarkers, only TP53 and ATRX mutations were significant poor prognosticators and only TP53 mutation was significant after multivariate analyses (p = 0.024). We conclude that IDH wildtype, H3 wildtype pediatric hemispheric glioblastomas are molecularly heterogeneous and in routine practice, TP53, ATRX, and MMR status could profitably be screened for risk stratification in laboratories without ready access to methylation profiling.
Journal
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • NTRK (Neurotrophic receptor tyrosine kinase)
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TP53 mutation • BRAF V600E • BRAF V600 • EGFR amplification • CDKN2A deletion • ALK fusion • MYCN amplification • ATRX mutation • TERT promoter mutation • TERT mutation • IDH wild-type
2ms
Chiauranib for Relapsed/Refractory Small Cell Lung Cancer (clinicaltrials.gov)
P1b/2, N=36, Recruiting, Chipscreen Biosciences, Ltd. | Not yet recruiting --> Recruiting
Enrollment open
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
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chiauranib (CS 2164)
2ms
APR-246, which restores p53 function, is highly active against alternative lengthening of telomere (ALT) cell lines and PDXs (AACR 2022)
ALT cancers of a variety of histologies are highly resistant to DNA damaging agents, have p53LOF, and constitutive activation of ATM kinase, which confers high sensitivity to p53 reactivation by APR-246. APR-246 warrants clinical testing in patients with ALT cancers.
Preclinical
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ATRX (ATRX Chromatin Remodeler) • TP53BP1 (Tumor Protein P53 Binding Protein 1) • CDKN1A (Cyclin-dependent kinase inhibitor 1A) • TERF2 (Telomeric Repeat Binding Factor 2)
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TP53 mutation • ATM mutation • ATRX mutation • TP53 overexpression
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irinotecan • eprenetapopt (APR-246)
3ms
Mutational Landscape and Outcomes of Conjunctival Melanoma in 101 Patients (WEC 2022)
This study confirms the high frequency of previously documented BRAF and NRAS mutations and recently reported ATRX and NF1 mutations in conjunctival melanoma. NRAS mutation implied increased risk for metastasis and death.
Clinical
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BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler)
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NRAS mutation • BRAF mutation • NF1 mutation • ATRX mutation • NRAS mutation + BRAF mutation
3ms
Experimental models of undifferentiated pleomorphic sarcoma and malignant peripheral nerve sheath tumor. (PubMed, Lab Invest)
Targeted sequencing analysis of a panel of genes frequently mutated in sarcomas identified TP53, RB1, and ATRX mutations in a subset of the cell lines. These new cellular models provide the scientific community with powerful tools for detailed studies of tumorigenesis and for investigating novel therapies for UPS and MPNST.
Journal
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TP53 (Tumor protein P53) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation
3ms
PROspect: The Study of Olaparib in Newly Diagnosed mCRPC Patients With HRR Gene Mutation (clinicaltrials.gov)
P2, N=30, Recruiting, Sun Yat-Sen Memorial Hospital of Sun Yat-Sen University
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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PALB2 mutation • CDK12 mutation • ATRX mutation • BRIP1 mutation • CHEK2 mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib)
3ms
Precision Medicine for IDH-mutant Diffuse Glioma(Lower-grade Glioma) (PubMed, No Shinkei Geka)
Besides these inhibitors, other strategies for targeting IDH mutations, such as immunotherapy and therapy targeting aberrant metabolic pathways resulting from IDH mutation are also examined. These novel therapies will be beneficial to patients.
Journal • IO biomarker
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation • TERT promoter mutation • TERT mutation
3ms
TERT expression increases with tumor grade in a cohort of IDH-mutant gliomas. (PubMed, Am J Transl Res)
Using immunohistochemical staining, we showed that controlling for ATRX and IDH mutational status, TERT expression increased with tumor grade in a cohort of patient-derived astrocytoma, anaplastic astrocytoma, and secondary glioblastoma samples. These findings indicate that TERT expression increases as astrocytomas become more aggressive tumors, and probably plays a role in their progression.
Journal
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TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
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ATRX mutation • TERT mutation
3ms
Bronchial Carcinoids: From Molecular Background to Treatment Approach. (PubMed, Cancers (Basel))
These options include somatostatin analogues, everolimus, peptide receptor radionuclide therapy, chemotherapy, radiotherapy, antiangiogenic agents, and immunotherapy. In this article, we provide a comprehensive review about the molecular and genetic background of BCs, and about the treatment of local and metastatic disease, as well as the main paraneoplastic syndromes that have been associated with this tumor.
Review • Journal • IO biomarker
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ATRX (ATRX Chromatin Remodeler) • MEN1 (Menin 1)
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ATRX mutation • MTOR mutation
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everolimus
3ms
Age influences on the molecular presentation of tumours. (PubMed, Nat Commun)
These effects are most striking in brain cancers where alterations like SUFU loss and ATRX mutation are age-dependent prognostic biomarkers. Using three cancer datasets, we show that age shapes the somatic mutational landscape of cancer, with clinical implications.
Journal
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CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler) • CREBBP (CREB binding protein)
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CDKN2A mutation • ATRX mutation • CREBBP mutation
3ms
Identification of Immune-Related lncRNA Prognostic Signature and Molecular Subtypes for Glioblastoma. (PubMed, Front Immunol)
GSs with poor survival were mainly infiltrated by mesenchymal stem cells (MSCs) and astrocyte, and were more sensitive to gefitinib and roscovitine. Among GSs, three hub genes KRT8, NGFR, and TCEA3, were screened and validated to potentially play feasible oncogenic roles in GBM. Construction of lncRNAs risk model and identification of GBM subtypes based on 17 irlncRNAs, which suggesting that irlncRNAs had the promising potential for clinical immunotherapy of GBM.
Journal • IO biomarker
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EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • NGFR (Nerve Growth Factor Receptor) • H19 (H19 Imprinted Maternally Expressed Transcript) • PLAU (Plasminogen Activator) • TCEA3 (Transcription Elongation Factor A3)
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EGFR mutation • ATRX mutation
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gefitinib • seliciclib (CYC202)
3ms
SGT-53 in Children With Recurrent or Progressive CNS Malignancies (clinicaltrials.gov)
P1, N=6, Not yet recruiting, SynerGene Therapeutics, Inc. | Trial completion date: Dec 2023 --> Dec 2024 | Trial primary completion date: Dec 2022 --> Dec 2023
Trial completion date • Trial primary completion date
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MGMT (6-O-methylguanine-DNA methyltransferase) • MDM2 (E3 ubiquitin protein ligase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
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ATRX mutation • MDM2 mutation
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Avastin (bevacizumab) • temozolomide • irinotecan • Onivyde (nanoliposomal irinotecan) • SGT-53
4ms
BAY1895344, a novel ataxia telangiectasia and RAD3-related (ATR) inhibitor, is active in vivo against ATRX mutated uterine leiomyosarcoma (SGO 2022)
Learning Objective: Identify the clinical potential of BAY1895344 in ATRX-mutated uterine leiomyosarcomas.
Preclinical
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
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elimusertib (BAY 1895344)
4ms
Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
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IDH1 mutation • ATRX mutation
4ms
Reliability of IDH1-R132H and ATRX and/or p53 immunohistochemistry for molecular subclassification of Grade 2/3 gliomas. (PubMed, Brain Tumor Pathol)
Moreover, there were three confusing cases with ATRX mutations but with retained ATRX-IHC positivity. The lessons learned from this study are as follows: (1) ATRX-IHC and p53-IHC should be supplementary to morphological diagnosis, (2) rare IDH mutations other than IDH1 R132H should be considered, and (3) there is no complete alternative test to detect molecular features of glioblastoma under the 2021 WHO classification.
Journal
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
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IDH1 mutation • ATRX mutation • IDH1 R132H • IDH1 R132
4ms
Association of MGMT Gene Promoter Methylation With Clinicopathological Parameters in Patients With Wild-type IDH Glioblastoma. (PubMed, Anticancer Res)
We suggest a possible association between MGMT methylation status and ATRX mutations in GBM with wild-type IDH.
Clinical • Retrospective data • Journal
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MGMT (6-O-methylguanine-DNA methyltransferase) • ATRX (ATRX Chromatin Remodeler)
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ATRX mutation • MGMT promoter methylation • IDH wild-type
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temozolomide
5ms
New P2 trial
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BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDK12 (Cyclin dependent kinase 12) • CHEK2 (Checkpoint kinase 2) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • CHEK1 (Checkpoint kinase 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • BARD1 (BRCA1 Associated RING Domain 1) • FANCL (FA Complementation Group L)
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PALB2 mutation • CDK12 mutation • ATRX mutation • BRIP1 mutation • CHEK2 mutation • RAD51D mutation • RAD51B mutation • BARD1 mutation • RAD54L mutation • RAD51 mutation • CHEK1 expression
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Lynparza (olaparib) • abiraterone acetate • prednisone
6ms
IS METHYLATION STATUS SUBGROUPING REALLY A STRONG PROGNOSTIC FACTOR IN PEDIATRIC POSTERIOR FOSSA EPENDYMOMA? (EHOC 2021)
There are no significant differences between PFAs and PFBs in terms of resection rates, disease recurrence and survival parameters.Patients with total surgical excisions had significantly better PFS and OS rates.Conclusion Extent of surgical excision is the most important prognostic indicator in PFEs. Prognostic effect of methylation subgrouping may be minimized with more aggressive surgical strategy in PFAs.
Clinical
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
6ms
ATRX regulates glial identity and the tumor microenvironment in IDH-mutant glioma. (PubMed, Genome Biol)
These studies explain how IDH-mutant gliomas from different subtypes maintain distinct phenotypes and tumor microenvironments despite a common lineage hierarchy.
Journal
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
6ms
Differences in the immune microenvironment of gliomas harboring IDH2 versus IDH1 mutations (SNO 2021)
IDH2 -mutant gliomas appeared to have a more immunosuppressive tumor microenvironment than their IDH1 -mutant counterparts. Early-phase immunotherapy trials should consider covariate-adaptive randomization approaches to equally allocate IDH2 -mutant gliomas across treatment arms.
IO biomarker
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CD8 (cluster of differentiation 8) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • CD4 (CD4 Molecule)
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TP53 mutation • IDH1 mutation • IDH2 mutation • ATRX mutation • TERT mutation
6ms
Direct in vivo CRISPR screen identifies cooperating tumor suppressors that drive progression of IDH1-mutant low-grade glioma to aggressive glioblastoma (SNO 2021)
Interestingly, Idh1 R132H did not alter tumor latency or pathology in a high grade p53;Pten;Rb1 mutant background, indicating that the neomorphic IDH-mutations can drive low but not high grade glioma development. Our study provides a functional landscape of gliomagenesis suppressors in vivo .
Preclinical
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TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NOTCH1 (Notch 1) • RB1 (RB Transcriptional Corepressor 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ATRX (ATRX Chromatin Remodeler) • FAT1 (FAT atypical cadherin 1) • BCOR (BCL6 Corepressor)
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TP53 mutation • IDH1 mutation • PTEN mutation • RB1 mutation • ATRX mutation • IDH1 R132H • IDH1 R132
6ms
Genetic Variation between IDH Mutant and IDH Wild-type Glioma (SNO 2021)
In IDH wild-type patients, patients with PTEN mutation have a worse prognosis. CONCLUSION There is an obvious genetic difference between IDH mutation and IDH wild-type glioma, and PTEN mutation is a poor prognostic factor for IDH wild-type patients.
Tumor Mutational Burden
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BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler) • SYNE1 (Spectrin Repeat Containing Nuclear Envelope Protein 1)
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TP53 mutation • BRAF mutation • PTEN mutation • NF1 mutation • ATRX mutation • TP53 expression
6ms
Feasibility of Single-Pass Stereotactic Needle Biopsy in Recurrent Glioblastoma Patients to Support CLIA-Certified Tumor Pharmacodynamics for a Phase 0/2 Clinical Trial (SNO 2021)
Based on IHC and genetic analyses of the biopsied samples, three patients were enrolled into the Phase 0/2 clinical trial and baseline value were used for PD analysis. CONCLUSION Single-pass stereotactic needle biopsy is a feasible and safe strategy to collect pre-treatment tissue in support of a Phase 0 clinical trial, enabling CLIA-certified genetic analysis for trial screening and tumor PD analysis.
Clinical • PK/PD data
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TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • PTEN mutation • CDKN2A deletion • ATRX mutation • ATRX deletion
6ms
Endogenous DNA double strand breaks activate heterogenous DNA damage signaling in IDH1/2 mutant gliomas (SNO 2021)
Interestingly, ALT+ GBM196 cells were highly vulnerable to inhibitors of ATM and ATR pathways. In conclusion, IDH1/TP53/ATRX mutant gliomas can be subdivided into HR-mediated ALT-positive group, which repairs the endogenous DSBs by HR (e.g. GBM196) and an ALT-negative/p-DNA-PK group, which repairs DSBs by c-NHEJ (e.g. GBM164) and this subdivision can be developed as a prescient biomarker of sensitivity to DDR inhibitors.
BRCA Biomarker
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TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • MRE11A (MRE11 homolog, double strand break repair nuclease) • TP53BP1 (Tumor Protein P53 Binding Protein 1)
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TP53 mutation • IDH1 mutation • ATRX mutation
6ms
[VIRTUAL] Differences in the Mutation of DAXX, ATRX, and MENIN in Pancreatic Neuroendocrine Tumors from Black and White Patients (NANETS 2021)
The significant difference in loss of MENIN in specimens from Black patients supports the hypothesis that differential epigenetic modulation may be occurring in pNETs arising in this population.
Clinical
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ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)
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ATRX mutation
6ms
ATR-X syndrome: genetics, clinical spectrum, and management. (PubMed, Hum Genet)
Finally, we propose a shift in the diagnosis of ATR-X patients, from a clinical diagnosis to a molecular-based approach. This may assist clinicians in patient management, risk assessment and genetic counseling.
Clinical • Review • Journal
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
7ms
Molecular classification and stratification of adult diffuse gliomas: A tertiary care center study. (PubMed, J Carcinog)
The results of the present study indicate that IHC including IDH1/2, ATRX, and p53 is useful for the molecular classification of diffuse gliomas, which could be useful for the evaluation of prognosis, especially Grade III and II. Although the immunohistochemical approach does not replace genetic testing completely, it is a practical and powerful means of assessing molecular genetic changes. IDH mutations are the established markers of better prognosis in diffuse gliomas.
Clinical • Journal
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • IDH1 mutation • ATRX mutation • TP53 overexpression
7ms
Clinicopathological Significance of ATRX Expression in Nasopharyngeal Carcinoma Patients: A Retrospective Study. (PubMed, J Cancer)
However, patients with negative ATRX expression had earlier T staging (P=0.045) and a higher 5-year overall survival (84.9% vs 66.9%, P=0.022). Loss of ATRX expression may contribute to better prognosis in patients with NPC.
Retrospective data • Journal
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ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
7ms
Enrollment open
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
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IDH2 mutation • ATRX mutation
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Zejula (niraparib)
7ms
History of atopy confers improved outcomes in IDH mutant and wildtype lower grade gliomas. (PubMed, J Neurooncol)
A history of atopy confers a survival benefit in patients with diffuse low-grade glioma. Activation of the BDNF pathway may drive the observed differences.
Journal
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TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • BDNF (Brain Derived Neurotrophic Factor)
|
ATRX mutation
7ms
[VIRTUAL] Machine Learning-Based Prediction of Survival Outcome in Lower Grade Gliomas With Combined Clinical and DNA Methylation Data (ASTRO 2021)
The combination of clinical and methylation data achieves a remarkable accuracy in predicting overall survival outcome in LGG patients, with highest overall class recall. The class recall (true positive rate or sensitivity) for deceased patients of combined data is superior to both clinical data-only and methylation data-only based analysis.
Clinical • Epigenetic controller
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TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation
7ms
Molecular Pathology of Gliomas. (PubMed, Surg Pathol Clin)
Focal amplifications of receptor tyrosine kinase genes, TERT promoter mutation, and loss of chromosomes 10 and 13 with trisomy of chromosome 7 are characteristic features of glioblastoma and can be used for diagnosis. BRAF gene fusions and mutations in low-grade gliomas and histone H3 mutations in high-grade gliomas also can be used for diagnostics.
Review • Journal
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • BRAF mutation • ATRX mutation • TERT promoter mutation • TERT mutation
7ms
Machine Learning-Based Prediction of Survival Outcome in Lower Grade Gliomas With Combined Clinical and DNA Methylation Data. (PubMed, Int J Radiat Oncol Biol Phys)
The combination of clinical and methylation data achieves a remarkable accuracy in predicting overall survival outcome in LGG patients, with highest overall class recall. The class recall (true positive rate or sensitivity) for deceased patients of combined data is superior to both clinical data-only and methylation data-only based analysis.
Clinical • Journal • Epigenetic controller
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation
7ms
The efficacy of immunohistochemistry in the diagnosis of molecular genetic alterations in central nervous system gliomas: Next-generation sequencing of 212 mutations in 112 patients. (PubMed, Clin Neuropathol)
Our single-center study suggests that IHC for IDH1/R132H, BRAF/V600E, and H3/K27M is highly reliable and may be used confidently in clinical practice. IHC for p53 and ATRX mutations is often reliable but possibly problematic, and genetic studies may be necessary to determine astrocytic or oligodendroglial differentiation.
Journal • Clinical • Next-generation sequencing
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BRAF (B-raf proto-oncogene) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • BRAF V600E • BRAF V600 • ATRX mutation • IDH1 R132H
|
Tempus xT Assay
7ms
Molecular Profile of a Pituitary Rhabdomyosarcoma Arising From a Pituitary Macroadenoma: A Case Report. (PubMed, Front Endocrinol (Lausanne))
Molecular profiling of the tumor identified mutations in TP53, ATRX, LZTR1, and NF1. Despite its rarity, characterization of pituitary RMS with immunohistochemistry and molecular studies may provide an insight to its pathophysiological relationship with pituitary adenoma.
Clinical • Journal
|
TP53 (Tumor protein P53) • NF1 (Neurofibromin 1) • ATRX (ATRX Chromatin Remodeler) • LZTR1 (Leucine Zipper Like Transcription Regulator 1)
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TP53 mutation • NF1 mutation • ATRX mutation
7ms
New P1 trial
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • PARP1 (Poly(ADP-Ribose) Polymerase 1)
|
IDH2 mutation • ATRX mutation
|
Zejula (niraparib)
8ms
Long-Term Report of a Comprehensive Molecular and Genomic Analysis in NRG Oncology/RTOG 0424: A Phase II Study of Radiation and Temozolomide in High-Risk Grade II Glioma. (PubMed, JCO Precis Oncol)
This study reports the long-term prognostic effect of the WHO molecular subgroups, MGMT promoter methylation, and other mutations in NRG/RTOG 0424. These results demonstrate that the WHO molecular classification and MGMT both serve as strong prognostic indicators, but that MGMT does not appear to add statistically significant prognostic value to the WHO subgrouping, above and beyond IDH and 1p/19q status.
P2 data • Journal
|
TP53 (Tumor protein P53) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • ATRX mutation • MGMT promoter methylation
|
temozolomide
8ms
Transcriptomic Landscape of Lower Grade Glioma Based on Age-Related Non-Silent Somatic Mutations. (PubMed, Curr Oncol)
Patients with the double mutation showed poorer prognosis than those with the double wild type genotype. Unlike IDH1 mutant, IDH1 wild-type showed upregulation of expression of epithelial mesenchymal transition associated genes.
Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • EGFR mutation • IDH1 mutation • ATRX mutation
8ms
How Do Telomere Abnormalities Regulate the Biology of Neuroblastoma? (PubMed, Biomolecules)
Patients with HRNB frequently present with widely metastatic disease, with tumors harboring recurrent genetic aberrations (MYCN amplification, TERT rearrangements, and ATRX mutations), which are mutually exclusive and capable of promoting TMM. This review provides recent insights into our understanding of TMM in NB tumors, and highlights emerging therapeutic strategies as potential treatments for telomerase- and ALT-positive tumors.
Review • Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
|
MYCN amplification • ATRX mutation • TERT amplification • TERT rearrangement
8ms
A Genome-Wide Profiling of Glioma Patients with an IDH1 Mutation Using the Catalogue of Somatic Mutations in Cancer Database. (PubMed, Cancers (Basel))
There was also significant over-expression of genes such as NDRG3 and KCNB1 in IDH1-mutant astrocytoma patients. We conclude that IDH1-mutant glioma is characterized by significant genetic changes that could contribute to a better prognosis in glioma patients.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • NOTCH1 (Notch 1) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2)
|
TP53 mutation • IDH1 mutation • PTEN mutation • ATRX mutation
9ms
Joint Modeling of RNAseq and Radiomics Data for Glioma Molecular Characterization and Prediction. (PubMed, Front Med (Lausanne))
Finally, we compare the performance of the proposed three mutation prediction radiogenomics-NB models with different well-known methods in the literature: Negative Binomial Linear Discriminant Analysis (NBLDA), differentially expressed RNAseq with Random Forest (RF-genomics), radiomics and differentially expressed RNAseq with Random Forest (RF-radiogenomics), and Voom-based count transformation combined with the nearest shrinkage classifier (VoomNSC). Our analysis shows that the proposed radiogenomics-NB model significantly outperforms (ANOVA test, p < 0.05) for prediction of IDH and ATRX mutations and offers similar performance for prediction of 1p/19q codeletion, when compared to the competing models in the literature, respectively.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
9ms
BICD Cargo Adaptor 1 (BICD1) Downregulation Correlates with a Decreased Level of PD-L1 and Predicts a Favorable Prognosis in Patients with IDH1-Mutant Lower-Grade Gliomas. (PubMed, Biology (Basel))
Intriguingly, we found a significant correlation between BICD1 downregulation and a decreased level of CD274, GSK3B, HGF, or STAT3 in LGGs. Our findings suggest that BICD1 downregulation could be a potential biomarker for a favorable prognosis of LGGs.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • HIF1A (Hypoxia inducible factor 1, alpha subunit) • ATRX (ATRX Chromatin Remodeler) • STAT3 (Signal Transducer And Activator Of Transcription 3) • BICD1 (BICD Cargo Adaptor 1)
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TP53 mutation • EGFR mutation • IDH1 mutation • ATRX mutation • HIF1A expression
9ms
Intracranial high-grade glioma with malignant progression of spinal intramedullary metastasis: an atypical presentation with review of literature. (PubMed, Br J Neurosurg)
In this case, the primary histopathological diagnosis post cranial tumour removal was Grade-3 anaplastic astrocytoma, whereas Spinal autopsy report done 16 months after the primary diagnosis showed Grade-4 GBM suggestive of secondary transformation (Secondary GBM), it showed same genome of IDH mutation and ATRX loss, neoplastic fibrillary and gemistocytic astrocytes with de-differentiation, foamy histiocytes as seen in primary lesion suggestive of progression and metachronicity rather than multicentricity or synchronicity. What is more peculiar and rare in our case is that the spinal disease was very malignant and it progressed in course of just two days to involve the whole spine.Key pointsMalignant ultra-rapid progression of spinal metastasis.Thorough review of literatureMetachronicity of spinal metastasisImportance of the studyThis study presents a very atypical case of malignant progression of spinal metastasis documented with successive MRI radiology scans in a span of mere two days.It is different from other studies in the sense such malignant progression in a span of few days has never been documented with radiographs.This manuscript also provides an exhaustive review of literature and draws comparisons among the same.This study compares→ Time period to diagnosis of spinal metastasis following primary diagnosis, Outcome from diagnosis of spine metastasis, age along with other variables like histopathology of spinal metastasis if available, Treatment underwent, site of metastasis among different studies.
Review • Journal
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ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
10ms
[VIRTUAL] Histone 3 thrimetilated in lysin 27 (H3K27me3) immunostaining is a diagnostic and prognostic marker in diffuse gliomas with mixed or oligodendroglial morphology (ECP 2021)
A diagnostic workflow including H3K27me3 immunostain- ing, after the assessment of IDH1/2 mutational status and ATRX staining, is useful to reduce the number of diffuse gliomas that necessitate 1p/19q codeletion testing. According to this algorithm, gliomas IDH-wt and IDH-mutant with ATRX loss are classified astrocytic; gliomas IDH-mutant with ATRX retention and H3K27me3 loss are classified oligodendroglial; only glio- mas IDH-mutant with retained or non-conclusive ATRX and retained H3K27me3 necessitate 1p/19q codeletion testing. H3K27me3 loss is as- sociated with longer recurrence-free survival.
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
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ATRX mutation • IDH1 R132H
10ms
Histone H3.3 G34-mutant Diffuse Gliomas in Adults. (PubMed, Am J Surg Pathol)
The distinct pathologic and molecular features of H3.3 G34-mutant diffuse gliomas in adult patients demonstrated the clinical importance of detecting H3.3 G34R/V mutations. The dismal prognosis of this rare high-grade glioma disease we reported here would further promote the investigation of dedicated therapeutic strategies.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • H3F3A (H3 Histone Family Member 3A)
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TP53 mutation • EGFR mutation • EGFR amplification • ATRX mutation • MGMT promoter methylation • PDGFRA mutation • TP53 expression • TERT promoter mutation • TERT mutation
10ms
Comprehensive Molecular Analyses of a Novel Mutational Signature Classification System with Regard to Prognosis, Genomic Alterations, and Immune Landscape in Glioma. (PubMed, Front Mol Biosci)
A nomogram with excellent performance was also developed for assessing the prognosis of patients with glioma. Our results can enhance the mastery of molecular features and facilitate the precise treatment and clinical management of glioma.
Journal • IO biomarker
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • IDH1 mutation • PTEN mutation • FGFR1 mutation • ATRX mutation
10ms
The genomic characteristics of different progression patterns in advanced non-small cell lung cancer patients treated with immune checkpoint inhibitors. (PubMed, Ann Transl Med)
Mutations in RAD54L (P=0.018) and MYC (P=0.04) were more common in FP patients; HPD patients showed more frequent RAD54L mutations (P<0.001). We demonstrated different genomic characteristics across different progression patterns following ICI treatment, which might assist clinicians in the prediction of a patient's response, identifying candidates for more effective ICI therapy.
Clinical • Journal • Checkpoint inhibition • Tumor Mutational Burden • IO biomarker
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EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • RET (Ret Proto-Oncogene) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • RAD54L (DNA Repair And Recombination Protein RAD54) • CDKN1B (Cyclin dependent kinase inhibitor 1B)
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KRAS mutation • EGFR mutation • HER-2 amplification • HER-2 mutation • MET amplification • EGFR amplification • RET fusion • ALK fusion • ALK mutation • MET mutation • ATRX mutation • ALK amplification • RAD54L mutation • NTRK1 mutation
11ms
Prognostic Significance of Altered ATRX/DAXX Gene in Pancreatic Neuroendocrine Tumors: A Meta-Analysis. (PubMed, Front Endocrinol (Lausanne))
Patients with altered ATRX/DAXX gene would have poor DFS according to the combined data. And altered ATRX/DAXX genes in metastatic patients showed a trend towards improved overall survival, although the difference did not reach statistical significance.
Retrospective data • Review
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ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)
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ATRX mutation
11ms
Molecular diagnostics helps to identify distinct subgroups of spinal astrocytomas. (PubMed, Acta Neuropathol Commun)
DMG-H3 tend to develop in adolescence with a similar dismal prognosis like GBM and HAP in the elderly. We here describe spinal HAP with a distinct molecular profile for the first time.
Journal
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PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler)
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PIK3CA mutation • CDKN2A deletion • ATRX mutation • ATRX deletion
11ms
H3K27me3 immunostaining is diagnostic and prognostic in diffuse gliomas with oligodendroglial or mixed oligoastrocytic morphology. (PubMed, Virchows Arch)
Furthermore, H3K27me3 retention was associated with significantly shorter relapse-free survival (P < 0.0001), independently from IDH mutation or 1p/19q codeletion (P < 0.005). Our data suggest that adding H3K27me3 immunostaining to the diagnostic workflow of diffuse gliomas with oligodendroglial or mixed morphology is useful for drastically reducing the number of cases requiring 1p/19q codeletion testing and providing relevant prognostic information.
Journal
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ATRX (ATRX Chromatin Remodeler)
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ATRX mutation
11ms
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • MMP9 (Matrix metallopeptidase 9)
|
TP53 mutation • EGFR mutation • IDH1 mutation • EGFR expression • ATRX mutation • MGMT promoter methylation • TERT mutation
11ms
Loss of ATRX confers DNA repair defects and PARP inhibitor sensitivity. (PubMed, Transl Oncol)
Taken together, these data reveal that ATRX may be used as a molecular marker for DDR defects and PARP inhibitor sensitivity, independent of IDH1/2 mutations. These data highlight the important role of common glioma-associated mutations in the regulation of DDR, and novel avenues for molecularly guided therapeutic intervention.
Journal • PARP Biomarker
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IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • ATR (Ataxia telangiectasia and Rad3-related protein)
|
IDH1 mutation • ATRX mutation
11ms
Characteristics of Patients ≥ 10 Years of Age with Diffuse Intrinsic Pontine Glioma: A Report from the International DIPG Registry. (PubMed, Neuro Oncol)
Patients ≥10 years old with DIPG have a median survival of 13 months. LTS present with longer symptom duration and are likely to be older at presentation compared to STS. ATRX mutation rates were higher in this population than the general DIPG population.
Clinical • Journal
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • ACVR1 (Activin A Receptor Type 1)
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TP53 mutation • IDH1 mutation • ATRX mutation
11ms
Impact of Immunohistochemical profiling of Glioblastoma multiforme on clinical outcomes: Real-world scenario in resource limited setting. (PubMed, Clin Neurol Neurosurg)
GBM patients treated with concurrent chemoradiation and those who completed the full Stupp-protocol experienced better survival outcomes. Molecular biology significantly impacts clinical outcomes and plays a key deterministic role in newer management strategies.
Clinical • Clinical data • Journal • Real-world evidence
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • IDH1 mutation • ATRX mutation • TP53 overexpression
|
temozolomide
12ms
[VIRTUAL] Pituitary Carcinoma with ATM and ATRX Mutations and a Clinically Significant Gain in the CCND2 Gene (AANP 2021)
Following the diagnosis, the patient was treated with capecitabine and temozolominde along with lanreotide...Abdominal imaging shows the pancreatic and liver masses to be stable. This case report highlights a rare neoplasm with poorly understood molecular features.
Clinical
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ATM (ATM serine/threonine kinase) • ATRX (ATRX Chromatin Remodeler) • CCND2 (Cyclin D2) • NCAM1 (Neural cell adhesion molecule 1) • SYP (Synaptophysin)
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ATRX mutation
|
capecitabine
12ms
[VIRTUAL] IDH-mutant Astrocytoma with EGFR Amplification – Case Series with Review of Literature (AANP 2021)
Case1 was a 59-year-old male with a right frontal tumor with IDH1R132H, TP53, and PIK3CA mutations; EGFR, PDGFRA, and KIT amplifications; and methylated MGMT; who expired two days after initiating temozolomide treatment... Co-existence of IDH mutation and EGFR amplification is occasionally seen in gliomas and should be considered in forthcoming classification paradigms. In our small series, all tumors carried the epigenetic signature of an IDH-mutant astrocytoma.
Clinical • Review
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EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MTAP (Methylthioadenosine Phosphorylase) • ATRX (ATRX Chromatin Remodeler)
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TP53 mutation • EGFR mutation • PIK3CA mutation • EGFR amplification • MYC amplification • KIT mutation • ATRX mutation • PDGFRA mutation • EGFR mutation + PIK3CA mutation
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temozolomide
12ms
[VIRTUAL] H3F3A G34 Mutation Frequency in High-grade IDH-wildtype Diffuse Glioma in Adult Patients (AANP 2021)
All evaluated cases (n=4) had complex genomes with partial to whole-arm gains and losses overall distinct from IDHWT-GBM. In conclusion, H3F3A G34 testing should be considered for 18-50 year-old patients, particularly in cases showing primitive morphology and/or loss of ATRX expression, while the negligible frequency of H3F3A G34 mutation in high-grade IDHWT-DG among patients >50 years indicates that tumors in this age group may be classified as IDHWT-GBM following a negative IDH result without additional H3F3A G34 testing, especially if ATRX protein expression is preserved.
Clinical
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TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ATRX (ATRX Chromatin Remodeler) • H3F3A (H3 Histone Family Member 3A)
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TP53 mutation • ATRX mutation • PDGFRA mutation
12ms
[VIRTUAL] Clinical Molecular Profiling of IDH-wildtype Glioblastoma Adult Patients: Old Patterns and New Insights (AANP 2021)
Presence of MGMTp methylation was similar between TERTpMUT and TERTpWT groups (34% versus 29%, p-value 0.38). Clinical molecular profiling of IDHWT-GBM recapitulates and expands the spectrum of previously reported patterns, underscoring the molecular heterogeneity of IDHWT-GBM and providing a valuable dataset to unravel novel patterns and associations.
Clinical
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EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • PTEN (Phosphatase and tensin homolog) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
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TP53 mutation • EGFR mutation • BRAF mutation • MET amplification • PTEN mutation • CDKN2A deletion • NF1 mutation • MET mutation • ATRX mutation • PDGFRA mutation • MET fusion • PPM1D mutation • TERT mutation
12ms
[VIRTUAL] A Case of POLE Mutation in High-grade Astrocytoma with Variant IDH1 Mutation R132C and Ultramutant Phenotype (AANP 2021)
This case shows that POLE mutations are not limited to IDH-wildtype gliomas. Correlation with germline testing, long-term follow-up, and additional cases will be needed to elucidate the clinical implications of POLE mutations in IDH-mutant astrocytomas.
Clinical • Tumor Mutational Burden • IO biomarker
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TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • POLE (DNA Polymerase Epsilon) • MGMT (6-O-methylguanine-DNA methyltransferase) • ATRX (ATRX Chromatin Remodeler) • GFAP (Glial Fibrillary Acidic Protein) • SYP (Synaptophysin)
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TP53 mutation • IDH1 mutation • POLE mutation • ATRX mutation • MGMT promoter methylation • IDH1 R132H • MSH2 mutation • IDH1 R132C
12ms
Systematic Analysis of 4-gene Prognostic Signature in Patients with Diffuse Gliomas Based on Gene Expression Profiles. (PubMed, J Cancer)
We established a malignant-related 4-gene molecular marker by glioma expression profile data from multiple microarrays and sequencing data. The four markers had good predictive power on the overall survival of glioma patients and were associated with gliomas' clinical and genetic backgrounds, including clinical features, gene mutation, methylation, CNV, signal pathways.
Clinical • Journal • Gene Expression Profile
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • TIMP1 (Tissue inhibitor of metalloproteinases 1) • TAGLN (Transgelin)
|
IDH1 mutation • ATRX mutation
12ms
Mutations inhibiting KDM4B drive ALT activation in ATRX-mutated glioblastomas. (PubMed, Nat Commun)
Conversely, KDM4B over-expression in ALT cancer cells abrogates ALT-associated features. In this work, we demonstrate that inactivation of KDM4B, through H3.3 or IDH1/2 mutations, acts in tandem with ATRX mutations to promote ALT in glioblastomas.
Journal
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • KDM4B (Lysine Demethylase 4B)
|
ATRX mutation
12ms
Unraveling Neuroendocrine Gallbladder Cancer: Comprehensive Clinicopathologic and Molecular Characterization. (PubMed, JCO Precis Oncol)
Our data provide insight into the development of NE GBC and suggest a common origin of precancerous epithelial lesions and invasive neuroendocrine components, favoring the hypothesis of lineage transformation. Moreover, nearly half of the NE GBCs carried at least one potentially actionable molecular alteration, highlighting the importance of molecular testing in this highly lethal cancer.
Clinical • Journal • Tumor Mutational Burden • BRCA Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • FGFR3 (Fibroblast growth factor receptor 3) • TACC3 (Transforming acidic coiled-coil containing protein 3) • MDM2 (E3 ubiquitin protein ligase) • RAD54L (DNA Repair And Recombination Protein RAD54)
|
TP53 mutation • HER-2 amplification • ATM mutation • ATRX mutation • FGFR3 fusion • RAD54L mutation
1year
Dissecting the impact of regional identity and the oncogenic role of human-specific NOTCH2NL in an hESC model of H3.3G34R-mutant glioma. (PubMed, Cell Stem Cell)
We also uncover a parallel mechanism of enhanced NOTCH2NL expression via genomic amplification of its locus in some H3.3G34R-mutant tumors. These findings demonstrate a novel mechanism whereby evolutionary pathways that lead to larger brain size in humans are co-opted to drive tumor growth.
Journal
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
1year
Re-evaluating tumors of purported specialized prostatic stromal origin reveals molecular heterogeneity, including non-recurring gene fusions characteristic of uterine and soft tissue sarcoma subtypes. (PubMed, Mod Pathol)
The present study shows that mesenchymal neoplasms of the prostate are morphologically and molecularly heterogeneous and include neoplasms that harbor genetic aberrations seen in specific mesenchymal tumors arising in other anatomic sites, including soft tissue and the uterus. These data suggest that tumors of purported specialized prostatic stromal origin may perhaps not represent a single diagnostic entity or specific disease group and that alternative diagnoses should be carefully considered.
Journal
|
TP53 (Tumor protein P53) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • ATRX (ATRX Chromatin Remodeler) • TPM3 (Tropomyosin 3) • BCOR (BCL6 Corepressor) • STAT6 (Signal transducer and activator of transcription 6)
|
ATRX mutation
1year
The association of sex-biased ATRX mutation in female gastric cancer patients with enhanced immunotherapy-related anticancer immunity. (PubMed, BMC Cancer)
ATRX mutation might serve as a potential predictive biomarker for favorable clinical benefit to ICI in female GC patients. ATRX mutation could be applied in combination with other biomarkers of ICI response to better identify the female GC patients who will derive greater benefits from ICI therapy.
Clinical • Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • IFNG (Interferon, gamma) • ATRX (ATRX Chromatin Remodeler)
|
PD-L1 expression • MSI-H/dMMR • ATRX mutation
1year
TEAD4 is a novel independent predictor of prognosis in LGG patients with IDH mutation. (PubMed, Open Life Sci)
Integrating TEAD4 CNV increase, IDH mutations, TP53 mutation, ATRX mutation and 1p19q co-deletion would separate patients with LGG into four groups with significant differences in prognosis. These study results suggested that TEAD4 variations were independent predictive biomarkers for the prognosis in patients with LGG with IDH mutation.
Clinical • Journal
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
1year
[VIRTUAL] MULTI-INSTITUTIONAL STUDY OF THE INCIDENCE AND OUTCOME OF PEDIATRIC IDH-MUTANT GLIOMA (ASPHO 2021)
A significant proportion of pediatric gliomas are characterized by IDH1/2 mutations, substantially higher among adolescents. Findings suggest that the natural history is similar to those of adult IDH-mutant gliomas, supporting consideration for adopting/incorporating adult treatment approaches.
Clinical
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
1year
Molecular biomarkers of response to eribulin in patients with leiomyosarcoma. (PubMed, Clin Cancer Res)
LMS has a complex genetic background, with multiple CNA and mutations affecting genes implicated in tumorigenesis. We identified several molecular changes with potential impact on survival of LMS patients when treated with eribulin.
Clinical • Journal
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • MUC16 (Mucin 16, Cell Surface Associated)
|
TP53 mutation • ATRX mutation • MUC16 mutation
|
Halaven (eribulin mesylate) • dacarbazine
1year
The Relationship between ASXL2 and ZBTB7A Gene Mutations and Prognosis in Patients with Acute Myeloid Leukemia (PubMed, Zhongguo Shi Yan Xue Ye Xue Za Zhi)
ASXL2 and ZBTB7A mutations are frequently found in t (8; 21) AML patients. The mutation of ASXL2 and ZBTB7A genes shows no significant effect on the prognosis of AML patients.
Clinical • Journal
|
ASXL1 (ASXL Transcriptional Regulator 1) • ATRX (ATRX Chromatin Remodeler) • BCOR (BCL6 Corepressor) • ZBTB7A (Zinc finger and BTB domain containing 7A)
|
ASXL1 mutation • ATRX mutation • BCOR mutation
1year
Treatment of Pediatric Adrenocortical Carcinoma With Surgery, Retroperitoneal Lymph Node Dissection, and Chemotherapy: The Children's Oncology Group ARAR0332 Protocol. (PubMed, J Clin Oncol)
Outcome for children with stage I ACC is excellent with surgery. Outcome for patients with stage II disease is inferior despite retroperitoneal lymph node dissection. Patients with stage III ACC have an excellent outcome combining surgery and chemotherapy. Patients with stage IV ACC are older and have a poor outcome; new treatments should be explored for this high-risk group. The combination of mitotane and chemotherapy as prescribed in ARAR0332 resulted in significant toxicity; one third of patients with advanced disease could not complete the scheduled treatment.
Clinical • Journal
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
|
Lysodren (mitotane)
1year
[VIRTUAL] Clinical stratification of pancreatic neuroendocrine tumors by systematically integrating multimodal and clinical data (ENETS 2021)
Our study helps to further understand directly tumor heterogeneity in relation to clinical parameters and multimodal data for potentially improved patient stratification.
Clinical data
|
ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)
|
ATRX mutation
1year
[VIRTUAL] A Novel Morphology-Based Risk Model Accurately Predicts Outcome in Stage I Uterine Leiomyosarcoma (USCAP 2021)
Multiple commonly evaluated morphologic parameters are independently associated with OS and DFS in stage I uLMS, including margin status, mitotic count, and coagulative necrosis. Tumor size is also independently associated with DFS. These parameters are clinically significant and should be routinely evaluated and reported for stage I uLMS.
RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • RB1 deletion
1year
[VIRTUAL] Mutations inhibiting KDM4B drive ALT telomere maintenance pathway in ATRX-mutated cancers (AACR 2021)
Conversely, KDM4B over-expression in ALT cancer cells abrogates ALT-associated features. Our data demonstrate that inactivation of KDM4B, either through H3.3G34R or IDH1/2 mutations, acts in tandem with ATRX mutations to promote ALT in cancers.
Clinical
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • KDM4B (Lysine Demethylase 4B)
|
ATRX mutation
1year
Meta-Analysis and Systematic Review of the Genomics of Mucosal Melanoma. (PubMed, Mol Cancer Res)
This analysis identified genomic aberrations that provide some insight to the way in which specific pathways may be disrupted. Implications: Our analysis has shown that mucosal melanomas have a diverse range of genomic alterations in several biological pathways.
Retrospective data • Review • Journal
|
BRAF (B-raf proto-oncogene) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • NF1 (Neurofibromin 1) • SF3B1 (Splicing Factor 3b Subunit 1) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • YAP1 (Yes associated protein 1) • ARID1B (AT-Rich Interaction Domain 1B) • MITF (Melanocyte Inducing Transcription Factor) • SKP2 (S-phase kinase-associated protein 2)
|
NRAS mutation • BRAF mutation • PTEN mutation • KIT mutation • SF3B1 mutation • ATRX mutation • CHEK2 mutation
1year
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=30, Active, not recruiting, Massachusetts General Hospital | N=223 --> 30
Enrollment change
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • MYC amplification • ARID1A mutation • CDK12 mutation • CCNE1 amplification • ATRX mutation • FBXW7 mutation • BRIP1 mutation • CHEK2 mutation • FANCA mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
|
berzosertib (M6620)
1year
Molecular landscape of IDH-mutant primary astrocytoma Grade IV/glioblastomas. (PubMed, Mod Pathol)
We conclude that IDH-mutant primary glioblastomas have better prognosis than secondary glioblastomas and have major molecular differences from other commoner glioblastomas. G-CIMP subgroups, MGMT promoter methylation, and TP53 mutation are useful prognostic adjuncts.
Journal
|
TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MGMT (6-O-methylguanine-DNA methyltransferase) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • EGFR amplification • CDKN2A deletion • ATRX mutation • MGMT promoter methylation • PDGFRA mutation • TERT promoter mutation • TERT mutation
1year
[VIRTUAL] Next-generation sequencing of the primary and recurrent tumors from patients with extranodal natural killer/T cell lymphoma (AACR 2021)
TSC2 is an FDA-recognized predictive marker for everolimus in central nervous system cancer and RAD54L is an FDA-recognized predictive marker for olaparib in prostate cancer. Our data showed that MUC16, ARID1A and ADAMTSL1 were observed in more than half of nasal-type ENKTL. Our data showed that MUC16, ARID1A and ADAMTSL1 were observed in more than half of nasal-type ENKTL. Additional mutations can be found in recurrent tumors but the relationship between the acquisition of new mutations and the treatment received was still poorly understood. TSC2 and RAD54L mutations were identified in some recurrent tumors which may serve as potential therapeutic targets for ENKTL.
Clinical • Next-generation sequencing • PARP Biomarker • IO biomarker
|
PTEN (Phosphatase and tensin homolog) • ARID1A (AT-rich interaction domain 1A) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • TSC2 (TSC complex subunit 2) • KMT2C (Lysine Methyltransferase 2C) • JAK1 (Janus Kinase 1) • FLT1 (Fms-related tyrosine kinase 1) • PIK3CG (Phosphatidylinositol-4,5-Bisphosphate 3-Kinase Catalytic Subunit Gamma) • FAT1 (FAT atypical cadherin 1) • CTLA4 (Cytotoxic T-Lymphocyte Associated Protein 4) • JAK3 (Janus Kinase 3) • ARID2 (AT-Rich Interaction Domain 2) • MUC16 (Mucin 16, Cell Surface Associated) • RAD54L (DNA Repair And Recombination Protein RAD54) • ABCC2 • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • CDKN1B (Cyclin dependent kinase inhibitor 1B) • FOXL2 (Forkhead Box L2)
|
PTEN mutation • ARID1A mutation • EZH2 mutation • ATRX mutation • TSC2 mutation • JAK3 mutation • RAD54L mutation • FAT1 mutation • NBN mutation
|
Lynparza (olaparib) • everolimus
1year
TMEFF2 promoter hypermethylation is an unfavorable prognostic marker in gliomas. (PubMed, Cancer Cell Int)
Our results suggest that TMEFF2 DNA methylation might be associated with glioma tumour progression and could serve as a valuable prognostic marker for adult diffuse gliomas.
Journal
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • EGF (Epidermal growth factor)
|
TP53 mutation • ATRX mutation
1year
Alternative lengthening of telomeres in childhood neuroblastoma from genome to proteome. (PubMed, Nat Commun)
ALT-positive neuroblastomas proliferate slowly, which is reflected by a protracted clinical course of disease. Nevertheless, children with an ALT-positive neuroblastoma have dismal outcome.
Clinical • Retrospective data • Journal
|
ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)
|
ATRX mutation
1year
Biological categories of neuroblastoma based on the international neuroblastoma pathology classification for treatment stratification. (PubMed, Pathol Int)
Abnormal maintenance/elongation of telomeres; overexpression of telomerase reverse transcriptase (TERT) and the alternative lengthening of telomeres (ALT) phenotype due to ATRX mutation, are another molecular event in UH. The INPC, incorporating immunohistochemistry for MYCN, MYC, ALK, TERT and ATRX, represents a practical and implementable approach to create the biological category for the future management of patients with this unique disease.
Review • Journal
|
ALK (Anaplastic lymphoma kinase) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
MYCN amplification • ATRX mutation • MYC positive • TERT overexpression
over1year
Diffuse midline glioma with H3 K27M mutation in the spinal cord: A series of 33 cases. (PubMed, Neuropathology)
In conclusion, H3 K27M mutation significantly predicts a worse outcome of spinal cord gliomas. Anatomical location and age are the main risk factors for DMGSCs.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
BRAF mutation • ATRX mutation • TP53 expression
over1year
DNA methylation patterns identify subgroups of pancreatic neuroendocrine tumors with clinical association. (PubMed, Commun Biol)
The T3 subgroup harboured mutations in MEN1 with recurrent loss of chromosome 11, was enriched for grade G1 tumors and showed histological parameters associated with better prognosis. Our results suggest a role for methylation in both driving tumorigenesis and potentially stratifying prognosis in PanNETs.
Clinical • Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
M6620 (VX-970) in Selected Solid Tumors (clinicaltrials.gov)
P2, N=223, Active, not recruiting, Massachusetts General Hospital | Recruiting --> Active, not recruiting
Enrollment closed
|
BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • CCNE1 (Cyclin E1) • CDK12 (Cyclin dependent kinase 12) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • ATRX (ATRX Chromatin Remodeler) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • RAD51B (RAD51 Paralog B) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • BARD1 (BRCA1 Associated RING Domain 1) • FANCF (FA complementation group F) • FANCM (FA Complementation Group M) • NBN (Nibrin Nijmegen Breakage Syndrome 1 (Nibrin)) • FANCC (FA Complementation Group C)
|
BRCA2 mutation • BRCA1 mutation • ATM mutation • MYC amplification • ARID1A mutation • CDK12 mutation • CCNE1 amplification • ATRX mutation • FBXW7 mutation • BRIP1 mutation • CHEK2 mutation • FANCA mutation • RAD51D mutation • RAD51C mutation • RAD51B mutation • BARD1 mutation • FANCF mutation • MRE11A mutation • NBN mutation • FANCM mutation
|
berzosertib (M6620)
over1year
[VIRTUAL] Long Intergenic Non Coding RNA and MicroRNA Profiles of Pheochromocytoma and Paraganglioma as Prognostic Biomarkers (ENDO 2021)
For oral presentations, the abstracts are embargoed until the session begins. The Endocrine Society reserves the right to lift the embargo on specific abstracts that are selected for promotion prior to or during ENDO 2021.
HIF1A (Hypoxia inducible factor 1, alpha subunit) • ATRX (ATRX Chromatin Remodeler) • SDHB (Succinate Dehydrogenase Complex Iron Sulfur Subunit B) • MIR182 (MicroRNA 182)
|
ATRX mutation
over1year
[VIRTUAL] Too much skin in the game? A paradigm shift in our understanding of vulvar and vaginal melanomas as distinct tumor types compared with cutaneous melanomas (SGO 2021)
VVM represents a distinct molecular profile from CM with a less favorable immune phenotype demonstrated by absence of TMB-high, lower rates of PD-L1 positivity, and lower adaptive immune gene expression and cell fractions of effector T-cells and immune promoting macrophages. Compared with CM, patients with VVM were found to have significantly worse survival when treated with IO therapy. Though IO has been a mainstay of treatment in recent years, these findings suggest that new therapeutic strategies are needed.
Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • SF3B1 (Splicing Factor 3b Subunit 1) • ATRX (ATRX Chromatin Remodeler)
|
PD-L1 expression • TMB-H • NRAS mutation • BRAF mutation • KIT mutation • SF3B1 mutation • ATRX mutation
|
PD-L1 IHC 28-8 pharmDx
over1year
BRAF Frequently Co-occurs With IDH1/2, TP53, and ATRX Mutations in Adult Patients With Gliomas and Is Associated With Poorer Survival Than That of Patients Harboring BRAF. (PubMed, Front Oncol)
Adult patients with glioma with BRAF and IDH1/2 had worse prognoses compared with those with BRAF mutation and BRAF and IDH1/2. This suggests that the assessment of the status of BRAF and IDH1/2 in adult glioma/glioblastoma patients has prognostic value as these patients have relatively short survival times and may benefit from personalized targeted therapy using BRAF and/or MEK inhibitors.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • BRAF V600E • BRAF mutation • BRAF V600 • IDH1 mutation • ATRX mutation • BRAF amplification
over1year
Alpha Thalassemia/Intellectual Disability X-Linked Deficiency Sensitizes Non-Small Cell Lung Cancer to Immune Checkpoint Inhibitors. (PubMed, Front Oncol)
The present study demonstrated that Atrx deficiency sensitize lung cancer cells to ICIs by multiple mechanisms. And ATRX may serve as a promising biomarker for ICIs which helps patient stratification and decision making.
Journal • Checkpoint inhibition • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • IFNG (Interferon, gamma) • ATRX (ATRX Chromatin Remodeler) • PTPRC (Protein Tyrosine Phosphatase Receptor Type C)
|
ATRX mutation
over1year
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 mutation • ATRX mutation
over1year
Salvage Radiation Therapy for Patients With Relapsing Glioblastoma Multiforme and the Role of Slow Fractionation. (PubMed, Front Oncol)
From 2009 until 2017, 124 of 218 patients received radical resection, adjuvant chemo-radiation with photons and temozolomide (TMZ) followed by adjuvant TMZ...Our observation challenges hypofractionated stereotactic radiotherapy for retreatment and controlled trials on the fractionation dose for SRT are needed. Robust predictive molecular markers could be beneficial in the selection of patients for SRT.
Clinical • Journal • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
|
temozolomide
over1year
A fully automated artificial intelligence method for non-invasive, imaging-based identification of genetic alterations in glioblastomas. (PubMed, Sci Rep)
Radiomics features extracted from fully automated deep learning-based tumor segmentations were used to predict nine common glioblastoma genetic biomarkers with random forest regression. The proposed fully automated method was useful for predicting IDH mutations (sensitivity = 0.93, specificity = 0.88), ATRX mutations (sensitivity = 0.94, specificity = 0.92), chromosome 7/10 aneuploidies (sensitivity = 0.90, specificity = 0.88), and CDKN2 family mutations (sensitivity = 0.76, specificity = 0.86).
Journal
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
Immunohistochemical expression of ATRX in gliomas. (PubMed, Cell Mol Biol (Noisy-le-grand))
No significant association was found between ATRX expression and patient's gender (p-value 0.097). It was found that ATRX is frequently expressed in grade II and III astrocytomas and was significantly related to the patient's age, tumor location, type and grade, so it can be used as a good diagnostic and prognostic indicator for glioma.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
Alternative lengthening of telomeres is the major telomere maintenance mechanism in astrocytoma with isocitrate dehydrogenase 1 mutation. (PubMed, J Neurooncol)
ALT is the major telomere maintenance mechanism in IDH mutated astrocytomas, while TERT promoter mutations were associated with IDH glioma. IDH1 downregulates ATRX expression in vitro resulting in ALT, which may contribute to the strong association of IDH1 mutations, ATRX loss, and ALT.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 mutation • ATRX mutation
|
doxycycline
over1year
An update on adult forms of hereditary pheochromocytomas and paragangliomas. (PubMed, Curr Opin Oncol)
A systematic genetic testing and counselling is recommended for all PPGL patients and should lead to conservative surgery and an adapted follow up, in case of hereditary form.
Clinical • Journal
|
TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
SGT-53 in Children With Recurrent or Progressive CNS Malignancies (clinicaltrials.gov)
P1, N=6, Not yet recruiting, SynerGene Therapeutics, Inc. | Trial completion date: Dec 2022 --> Dec 2023 | Trial primary completion date: Dec 2021 --> Dec 2022
Clinical • Trial completion date • Trial primary completion date
|
MGMT (6-O-methylguanine-DNA methyltransferase) • MDM2 (E3 ubiquitin protein ligase) • CDKN1A (Cyclin-dependent kinase inhibitor 1A)
|
ATRX mutation • MDM2 mutation
|
Avastin (bevacizumab) • temozolomide • irinotecan • Onivyde (nanoliposomal irinotecan) • SGT-53
over1year
Radiologic findings and the molecular expression profile of diffuse midline glioma H3 K27M mutant. (PubMed, Acta Radiol)
Cortical invasion, leptomeningeal tumor spread, lower ADC value and higher rCBV ratio in NE areas of DMG may be related to normal expression of ATRX.
Journal
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation • TP53 expression
over1year
Beyond the World Health Organization classification of central nervous system tumors 2016: what are the new developments for gliomas from a clinician's perspective? (PubMed, Curr Opin Neurol)
These changes increase diagnostic accuracy and refine clinical care by changing treatment recommendations, for example for patients with IDH-wildtype astrocytomas showing molecular features of glioblastoma. They also have major implications for clinical trial design.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
EGFR mutation • EGFR amplification • CDKN2A deletion • ATRX mutation
over1year
Current Clinical Practice About Pediatric Midline Gliomas in the Scope of Molecular Era. (PubMed, Turk Neurosurg)
Although most midline gliomas are not amenable to gross total excision, obtaining tissue samples is mandatory for determining patients? exact diagnoses, tailored treatment plans, and eligibility for clinical trials. Stereotactic biopsy for midline gliomas is a safe and effective method.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
BRAF V600E • BRAF V600 • EGFR amplification • ATRX mutation • EGFR mutation + PTEN mutation • PTEN loss
|
ONC201
over1year
[VIRTUAL] Two rare cases of IDH1-mutated gliosarcomas arising in IDH1-mutated, 1p/19q non-codeleted diffuse gliomas with prominent oligodendroglial morphology (ECP 2020)
Conclusion We report two IDH1-mutated gliosarcomas, arising in IDH1-mutated/ATRX-positive gliomas with oligodendroglial morphology and lack of 1p/19q codeletion. In one case, mutant-type p53 expression was acquired in sarcomatous component during progression of the tumour.
Clinical
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • SOX10 (SRY-Box 10) • GFAP (Glial Fibrillary Acidic Protein)
|
TP53 mutation • IDH1 mutation • ATRX mutation • IDH1 R132H • TP53 expression
over1year
[VIRTUAL] Two rare cases of IDH1-mutated gliosarcomas arising in IDH1-mutated, 1p/19q non-codeleted diffuse gliomas with prominent oligodendroglial morphology (ECP 2020)
Conclusion We report two IDH1-mutated gliosarcomas, arising in IDH1-mutated/ATRX-positive gliomas with oligodendroglial morphology and lack of 1p/19q codeletion. In one case, mutant-type p53 expression was acquired in sarcomatous component during progression of the tumour.
Clinical
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • SOX10 (SRY-Box 10) • GFAP (Glial Fibrillary Acidic Protein)
|
TP53 mutation • IDH1 mutation • ATRX mutation • IDH1 R132H • TP53 expression
over1year
[VIRTUAL] Two rare cases of IDH1-mutated gliosarcomas arising in IDH1-mutated, 1p/19q non-codeleted diffuse gliomas with prominent oligodendroglial morphology (ECP 2020)
Conclusion We report two IDH1-mutated gliosarcomas, arising in IDH1-mutated/ATRX-positive gliomas with oligodendroglial morphology and lack of 1p/19q codeletion. In one case, mutant-type p53 expression was acquired in sarcomatous component during progression of the tumour.
Clinical
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • SOX10 (SRY-Box 10) • GFAP (Glial Fibrillary Acidic Protein)
|
TP53 mutation • IDH1 mutation • ATRX mutation • IDH1 R132H • TP53 expression
over1year
The importance of IDH1, ATRX and WT-1 mutations in glioblastoma. (PubMed, Pol J Pathol)
There was no statistically significant difference in the progression-free and overall survival according to the surgical method. IDH1 and ATRX mutations, p53 overexpression and WT-1 expression alone did not have a significant effect on the prognosis of patients with glioblastoma; however, radiotherapy and chemotherapy had a positive effect on survival.
Journal
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • WT1 (WT1 Transcription Factor)
|
TP53 mutation • ATRX mutation
over1year
Pan-neuroblastoma analysis reveals age- and signature-associated driver alterations. (PubMed, Nat Commun)
Signature 18 is enriched in neuroblastomas with MYCN amplification, 17q gain, and increased expression of mitochondrial ribosome and electron transport-associated genes. Recurrent FGFR1 variants in six patients, and ALK N-terminal structural alterations in five samples, identify additional patients potentially amenable to precision therapy.
Journal
|
ALK (Anaplastic lymphoma kinase) • FGFR1 (Fibroblast growth factor receptor 1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
|
MYCN amplification • ATRX mutation
over1year
TERT promoter mutation associated with multifocal phenotype and poor prognosis in patients with IDH wild-type glioblastoma. (PubMed, Neurooncol Adv)
TERTp mutations were strongly correlated with multifocal/distant lesions and poor prognosis in patients with IDH wild-type GBM. Less aggressive GBM with TERTp wild type may be a distinct clinical and molecular subtype of IDH wild-type GBM.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • CD133
|
TP53 mutation • BRAF mutation • PTEN deletion • PTEN mutation • CDKN2A deletion • TP53 deletion • ATRX mutation
over1year
Alternative lengthening of telomeres in molecular subgroups of paediatric high-grade glioma. (PubMed, Childs Nerv Syst)
Our results show a strong association between H3.3 mutations and ALT, and highlight the different telomeric profiles in histone-defined subgroups: H3.3-G34R mutants always trigger ALT to maintain telomere length, irrespective of ATRX status, whereas only some H3.3-K27M tumours activate ALT. These findings suggest that acquiring the gly34 mutation on H3.3 might suffice to trigger the ALT mechanism.
Journal
|
TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • H3.3K27M
over1year
Integrated genomic and transcriptomic analysis revealed mutation patterns of de-differentiated liposarcoma and leiomyosarcoma. (PubMed, BMC Cancer)
Our analysis revealed different recurrent genetic variations in LMS and DDLPS including simultaneous upregulation of gene expression and gene copy number amplification of MDM2 and CDK4. Up-regulation of tumor related genes is favored in DDLPS, while loss of suppressor function is favored in LMS. DDLPS harbors more frequent fusion events which can generate neoepitopes and potentially targeted by personalized immune treatment.
Journal
|
HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • PTEN mutation • ATRX mutation • MDM2 overexpression
over1year
Multi-Phase Cross-modal Learning for Noninvasive Gene Mutation Prediction in Hepatocellular Carcinoma. (PubMed, Annu Int Conf IEEE Eng Med Biol Soc)
Considering intra-tumour heterogeneity (ITH) in HCC, multi-region sampling technology is implemented to generate the dataset for experiments. Experimental results demonstrate the effectiveness of the proposed model.
Journal
|
ATRX (ATRX Chromatin Remodeler) • APOB (Apolipoprotein B) • COL1A1 (Collagen, type I, alpha 1)
|
ATRX mutation
over1year
Corticotroph aggressive pituitary tumours and carcinomas frequently harbour ATRX mutations. (PubMed, J Clin Endocrinol Metab)
ATRX mutations occur in a subset of aggressive pituitary tumours and are more common in corticotroph tumours. The findings provide a rationale for performing ATRX immunohistochemistry to identify patients at risk of developing aggressive and potentially metastatic pituitary tumours.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
Successful resection of a neuroendocrine tumor in the gallbladder: a case report. (PubMed, Surg Case Rep)
We experienced a very rare case of GB-NET. Obtaining a correct preoperative diagnosis is quite difficult at the first evaluation. A GB-NET should be considered as a differential diagnosis of gallbladder tumors.
Clinical • Journal
|
ATRX (ATRX Chromatin Remodeler) • NCAM1 (Neural cell adhesion molecule 1)
|
ATRX mutation
over1year
Diffuse Astrocytoma with Malignant Progression after Long-term Temozolomide Monotherapy:A Case Report (PubMed, No Shinkei Geka)
Currently, multimodal therapy selection may be performed during initial treatment. Thus, an integrated diagnostic approach based on both histological and molecular findings is essential to identify the optimal treatment.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • IDH1 R132H
|
temozolomide
over1year
IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma: a case report. (PubMed, Br J Neurosurg)
However, this case showed that the other genetic mutations can be initiated before the IDH mutation in glioma oncogenesis. Contrary to the previous hypothesis, this is the first case of IDH-wildtype secondary glioblastoma arising in IDH-mutant diffuse astrocytoma.
Clinical • Journal
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • PTEN mutation • ATRX mutation
over1year
[VIRTUAL] Interplay between IDH1 and ATRX mutations govern innate immune responses in gliomas (SNO 2020)
On the other hand, presence of IDH1R132H led to a suppression in baseline expression of key innate immune players, which could be rescued by the mutant IDH1 inhibitor, BAY-1436032...Our data indicates the presence of an interplay between IDH1 and ATRX mutations that may regulate innate signaling in gliomas. Understanding the mechanisms governing this interplay may aid in designing therapies that exploit this interplay.
IO biomarker
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 mutation • ATRX mutation • IDH1 R132H
|
BAY1436032
over1year
[VIRTUAL] NEXT-GENERATION SEQUENCING OF GLIOBLASTOMA MULTIFORME ‘EXTREME RESPONDERS’ (SNO 2020)
Conclusion Acknowledging the fact that our sample size was small and no control group was tested, our study infers a higher incidence of IDH1, TP53 and ATRX mutations which are more common in secondary glioblastomas and this may be a contributing factor towards longer survival in our cohort. We did not identify any universal molecular marker predictive of improved prognosis or exquisite sensitivity to chemoradiotherapy.
Tumor Mutational Burden • Next-generation sequencing
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1)
|
TP53 mutation • IDH1 mutation • ATRX mutation
|
FoundationOne® CDx
over1year
[VIRTUAL] ATRX deficiency in glioma impacts transcriptional profiles and the immune microenvironment in vivo (SNO 2020)
Finally, Atrx deficient murine gliomas displayedincreased levels of NK cells, a phenotype recapitulated in ATRX-mutant human gliomas, and primary Atrx-deficient glioma lines exhibited increased levels of NK cell-attracting cytokines. These latter findings suggest that ATRX deficiency could influence interactions between glioma cells and their immune microenvironment by way of phenotypically relevant molecular mechanisms.
Preclinical
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
[VIRTUAL] The deubiquitinase BRCC3 links ALT telomeres to suppression of innate immunity in IDH1-mutant glioma. (SNO 2020)
These results show that BRCC3 translocated along with ECTRs to the cytoplasm degrades cGAS and protects ALT-dependent cells from activating the innate immune response. The BRCC3-controlled cGAS-STING pathway may therefore represent a therapeutically targetable means to enhance the immune response in IDH1-mutant lower grade glioma.
PARP Biomarker
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • TERF2 (Telomeric Repeat Binding Factor 2)
|
IDH1 mutation • ATRX mutation • IFNG expression
over1year
Glioblastomas harboring gene fusions detected by next-generation sequencing. (PubMed, Brain Tumor Pathol)
Additionally, we described two novel cases of CCDC6-RET fusion in glioma. Collectively, our findings indicate that targetable gene fusions are associated with aggressive biological behavior and can aid the clinical treatment strategy for glioma patients.
Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • FGFR (Fibroblast Growth Factor Receptor) • TERT (Telomerase Reverse Transcriptase) • CCDC6 (Coiled-Coil Domain Containing 6) • ATRX (ATRX Chromatin Remodeler) • AKT3 (V-akt murine thymoma viral oncogene homolog 3) • NTRK (Neurotrophic receptor tyrosine kinase)
|
TP53 mutation • EGFR amplification • PTEN mutation • RET fusion • CCDC6-RET fusion • ATRX mutation • EGFR exon 2-7 deletion + EGFR amplification • MET fusion • EGFR mutation + PTEN mutation
over1year
Patient-derived organoids and orthotopic xenografts of primary and recurrent gliomas represent relevant patient avatars for precision oncology. (PubMed, Acta Neuropathol)
We show clinically relevant responses to temozolomide (TMZ) and to targeted treatments, such as EGFR and CDK4/6 inhibitors in (epi)genetically defined subgroups, according to MGMT promoter and EGFR/CDK status, respectively. Dianhydrogalactitol (VAL-083), a promising bifunctional alkylating agent in the current clinical trial, displayed high therapeutic efficacy, and was able to overcome TMZ resistance in glioblastoma. Our work underscores the clinical relevance of glioma organoids and PDOX models for translational research and personalized treatment studies and represents a unique publicly available resource for precision oncology.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • IDH1 mutation • EGFR amplification • CDKN2A deletion • ATRX mutation
|
temozolomide • dianhydrogalactitol (VAL-083)
over1year
Incidence of biomarkers in high-grade gliomas and their impact on survival in a diverse SouthEast Asian cohort - a population-based study. (PubMed, BMC Cancer)
The incidences of MGMT promoter methylation and IDH1 mutation were found to be comparable to globally reported rates, but those of 1p19q co-deletion and ATRX loss seemed to be lower in our cohort. MGMT promoter methylation was associated with increased overall survival in our cohort and might serve as favorable prognostic factor.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 mutation • ATRX mutation
over1year
H3 G34-mutant high-grade glioma. (PubMed, Brain Tumor Pathol)
The median survival of H3.3 G34-mutant HGGs was better than those of IDH-wildtype GBMs and H3 K27M-mutant DMGs, but worse than that of IDH-mutant GBM. The tumor-infiltrating area and resectability may be the crucial parameters for the prognosis of the patients.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
Reduced H3K27me3 levels in diffuse gliomas: association with 1p/19q codeletion and difference from H3K27me3 loss in malignant peripheral nerve sheath tumors. (PubMed, Brain Tumor Pathol)
H3K27me3 loss predicted 1p/19q codeletion in IDH-mutant gliomas with lower sensitivity (56.2%) and higher specificity (100%) than ATRX retention or p53 negative result. In conclusion, reduction in H3K27me3 levels was associated with 1p/19q codeletion in diffuse gliomas; however, the extent of reduction differed from that in MPNSTs, and the results depended on the immunostaining conditions.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
over1year
Telomere Maintenance Associated Mutations in the Genetic Landscape of Gynecological Mucosal Melanoma. (PubMed, Front Oncol)
Kaplan-Meier revealed that ALT relative to TERT amplification was associated with longer overall survival in GM patients without metastasis. These findings indicate that telomere maintenance mechanisms play a critical role in the tumorigenesis of GMs and may aid in the prediction of clinical prognosis and the development of targeted therapy for the treatment of GM.
Clinical • Journal
|
TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
Genomic Profiling Aids Classification of Diagnostically Challenging Uterine Mesenchymal Tumors With Myomelanocytic Differentiation. (PubMed, Am J Surg Pathol)
Integrating histopathologic, immunohistochemical, and genetic findings, tumors from 4 patients were consistent with malignant PEComa (1 TFE3-rearranged); 6 were classified as leiomyosarcomas; 3 showed overlapping features of PEComa and other sarcoma types (leiomyosarcoma or low-grade endometrial stromal sarcoma); and 2 were classified as sarcoma, not otherwise specified. Our findings suggest that diagnostically challenging UMTs with myomelanocytic differentiation represent a heterogenous group of neoplasms which harbor a diverse repertoire of somatic genetic alterations; these genetic alterations can aid classification.
Journal • BRCA Biomarker
|
TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • MITF (Melanocyte Inducing Transcription Factor)
|
TP53 mutation • BRCA2 mutation • CDKN2A deletion • FGFR3 mutation • ATRX mutation • RB1 deletion • BRCA2 deletion • TSC2 mutation • BRCA1 deletion
over1year
Comprehensive genomic profiling of gastroenteropancreatic neuroendocrine neoplasms (GEP-NENs). (PubMed, Clin Cancer Res)
Significant molecular differences were observed in GEP-NENs by tumor location and grade, indicating differences in carcinogenic pathways and biology.
Journal • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker
|
PD-L1 (Programmed death ligand 1) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • ARID1A (AT-rich interaction domain 1A) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • FOXO3 (Forkhead box O3)
|
TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • PD-L1 overexpression • BRAF mutation • ARID1A mutation • ATRX mutation • TMB + PD-L1 expression
over1year
Main genetic differences in high-grade gliomas may present different MR imaging and MR spectroscopy correlates. (PubMed, Eur Radiol)
• IDH1-wt tumours present higher levels of mobile lipids than IDH1-mut. • Mutated ATRX tumours exhibit higher levels of glutamate and glutamine. • Loss of p53 expression, Ki-67 expression, and glutamate and glutamine levels may contribute to the presence of an infiltrative pattern in HGG.
Journal
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • IDH1 mutation • ATRX mutation • TP53 expression
over1year
Risk Stratification in Low Grade Glioma: A Single Institutional Experience. (PubMed, Neurol India)
Taken together, the clinical symptoms, expression of molecular markers and the prognosis details provided by our results can help for better management of LGG cases. We further propose to use following five factors to accurately describe the prognosis and tumor recurrence: 1) Age >50 years, 2) tumor size >5 cm, 3) MIB index >5%, 4) KPS score < 70 and 5) gemistocytic pathology.
Clinical • Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
over1year
Therapeutic vulnerabilities in the DNA damage response for the treatment of ATRX mutant neuroblastoma. (PubMed, EBioMedicine)
ATRX LoF results in specific DNA damage repair defects that can be therapeutically exploited. In ATRX LoF models, preclinical sensitivity is demonstrated to olaparib and irinotecan, a combination that can be rapidly translated into the clinic.
Journal • PARP Biomarker
|
ATRX (ATRX Chromatin Remodeler)
|
ATM mutation • ATRX mutation
|
Lynparza (olaparib) • irinotecan • sapacitabine (CYC682)
over1year
Correlation between IDH, ATRX, and TERT promoter mutations in glioma. (PubMed, Brain Tumor Pathol)
Although the mechanism of how ATRX mutation induces ALT remains unclear, ATRX loss alone is believed to be insufficient to induce ALT. Treatments targeting telomere maintenance are promising.
Review • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
over1year
[VIRTUAL] PEDIATRIC HIGH GRADE GLIOMA RECURRENCE FOLLOWING TEMOZOLOMIDE WITH ACQUIRED MSH6 VARIANT AND HYPERMUTATION: A CASE REPORT (SIOP 2020)
Imaging showed residual tumor and she started maintenance therapy with irinotecan and bevacizumab, subsequently changed to bevacizumab and temozolomide, for a total of 13 cycles...The patient had initially started salvage therapy with CCNU and everolimus, however, given hypermutation, she was switched to pembrolizumab...Conclusions This case illustrates a G34R high grade glioma with acquired hypermutation and somatic MSH6 mutation following temozolomide in a pediatric patient, which has not been previously described. These findings resulted in a treatment change to immune checkpoint inhibition, though of unclear benefit.
Clinical • PD(L)-1 Biomarker • IO biomarker
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MSH6 (MutS homolog 6) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • PTEN mutation • ATRX mutation • PDGFRA mutation • MSH6 mutation
|
Keytruda (pembrolizumab) • Avastin (bevacizumab) • everolimus • temozolomide • irinotecan
over1year
[VIRTUAL] IDENTIFICATION OF GENETIC ALTERATIONS IN CHILDHOOD AND ADOLESCENCE GLIOBLASTOMA (GBM) USING NEXT GENERATION SEQUENCING STRATEGY. (SIOP 2020)
Conclusions Molecular profiling based on NGS genetic panel, specific for pediatric tumors, can provide information about potential prognostic biomarkers for GBM. Thus, wider understanding about GBM biologic heterogeneity may lead to personalized therapeutic strategies.
Clinical • Next-generation sequencing
|
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
almost2years
Is it a new culprit? "TERT promoter mutation" in an aggressive pediatric pilocytic astrocytoma. (PubMed, Childs Nerv Syst)
Recent advances in the genomic study have revolutionized the discovery of molecular biomarkers in glioma not only to aid in targeted therapy but also to prognosticate character of tumor and outcome of a patient.The usually benign nature of pilocytic astrocytoma (PA) can now be challenged with the discovery of genomic alterations that could promote more aggressive clinical behavior. CDKN2A deletion and ATRX gene inactivation or mutation have been the most common molecular alterations in worse prognosis.We will discuss a case of pilocytic astrocytoma showing the progressive recurrence with pilomyxoid features and the presence of TERT promoter mutation.
Clinical • Journal
|
CDKN2A (Cyclin-dependent kinase inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
CDKN2A deletion • ATRX mutation
almost2years
Clinical, radiological and molecular characterization of intramedullary astrocytomas. (PubMed, Acta Neuropathol Commun)
The H3F3A p.K27M mutation showed significant associations with OS and EFS after multivariate analysis. This study emphasizes that IMAs have distinct clinico-radiological, natural evolution and molecular landscapes from brain astrocytomas.
Clinical • Journal
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • KIAA1549
|
TP53 mutation • BRAF mutation • ATRX mutation • KIAA1549-BRAF fusion • BRAF fusion
almost2years
Actionable co-alterations in breast tumors with pathogenic mutations in the homologous recombination DNA damage repair pathway. (PubMed, Breast Cancer Res Treat)
HR-MT was common across breast cancer subtypes and co-occurred more frequently with markers of response to immunotherapy (MSI-H/dMMR, TMB) compared to HR-WT tumors. Mutations were identified in both HR-MT and HR-WT tumors that suggest other targets for treatment. Clinical trials combining HRD-targeted agents and immunotherapy are underway and could be enriched through comprehensive molecular profiling.
Journal • BRCA Biomarker • MSi-H Biomarker • PARP Biomarker • PD(L)-1 Biomarker
|
HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • ATM (ATM serine/threonine kinase) • ARID1A (AT-rich interaction domain 1A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • PALB2 (Partner and localizer of BRCA2) • BAP1 (BRCA1 Associated Protein 1) • KMT2D (Lysine Methyltransferase 2D) • ATRX (ATRX Chromatin Remodeler) • FANCA (FA Complementation Group A) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • RAD50 (RAD50 Double Strand Break Repair Protein) • CHEK1 (Checkpoint kinase 1) • MRE11A (MRE11 homolog, double strand break repair nuclease) • BARD1 (BRCA1 Associated RING Domain 1) • WRN (WRN RecQ Like Helicase)
|
BRCA1 mutation • MSI-H/dMMR • PD-L1 overexpression • PIK3CA mutation • ATM mutation • ARID1A mutation • BAP1 mutation • ATRX mutation • AR overexpression • BRIP1 mutation • FANCA mutation • RAD50 mutation • BARD1 mutation • BLM mutation • CHEK1 mutation • NBN mutation • PIK3CA overexpression • CHEK1 expression
almost2years
Infratentorial IDH-mutant astrocytoma is a distinct subtype. (PubMed, Acta Neuropathol)
The presented data highlight the very existence and distinctiveness of infratentorial IDH-mutant astrocytomas that have important implications for diagnostics and prognostication. They imply that molecular testing is critical for detection of these tumors, since many of these tumors cannot be identified by immunohistochemistry applied for the mutated IDH1-R132H protein or loss of ATRX.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 mutation • ATRX mutation • IDH1 R132H • IDH1 R132C • IDH2 R172
almost2years
Acquired ATRX Loss and ALT Phenotype Through Tumor Recurrences in a Case of Pleomorphic Xanthoastrocytoma Suggest Their Possible Roles in Tumor Progression. (PubMed, J Neuropathol Exp Neurol)
Our data not only confirm previous findings of the possible occurrence of ATRX mutations in PXA but also suggest that this alteration is linked to PXA progression. In small biopsies, tumors with ATRX loss, without IDH or histone mutation, pathologists should consider the diagnosis of PXA, especially if associated with BRAF V600E mutation, CDKN2A deletion, and ALT.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler)
|
BRAF V600E • BRAF V600 • CDKN2A deletion • CDKN2A mutation • ATRX mutation
almost2years
Genomic Database Analysis of Uterine Leiomyosarcoma Mutational Profile. (PubMed, Cancers (Basel))
Overall survival did not show significant correlation with the mutational status, even if RB1 mutation emerged as a favorable prognostic factor in the TP53-mutant subgroup. This comprehensive analysis shows that uLMS is driven almost exclusively by the inactivation of tumor suppressor genes and suggests that future therapeutic strategies should be directed at targeting the main genetic drivers of uLMS oncogenesis.
Journal
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • PTEN mutation • RB1 mutation • ATRX mutation
almost2years
Molecular Alterations in Vaginal Melanomas: Report of 4 Cases and Literature Review. (PubMed, Am J Dermatopathol)
In conclusion, in addition to KIT, TP53, and ATRX mutations, which have been previously reported, our cases harbor NF2 mutation and multiple gene copy alterations that have not previously been documented in vaginal melanomas. These findings highlight the potential role of targeted therapy in this rare melanoma subtype.
Clinical • Journal
|
TP53 (Tumor protein P53) • GNA11 (G Protein Subunit Alpha 11) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2)
|
TP53 mutation • KIT mutation • ATRX mutation • KIT L576P • NF2 mutation • TSC2 mutation
almost2years
A dual-genotype oligoastrocytoma with histologic, molecular, radiological and time-course features. (PubMed, Acta Neuropathol Commun)
Reports of the clinical courses for these rare cases of dual-genotype oligoastrocytomas will inform therapy choices, to optimize benefit while minimizing side effects. The steadily increasing number of cases suggests that the neoplasm might be reconsidered as an official entity by the WHO.
Journal
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
almost2years
Randomised phase II trial of CAPTEM or FOLFIRI as SEcond-line therapy in NEuroendocrine CArcinomas and exploratory analysis of predictive role of PET/CT imaging and biological markers (SENECA trial): a study protocol. (PubMed, BMJ Open)
The SEcond-line therapy in NEuroendocrine CArcinomas (SENECA) study is a randomised, non-comparative, multicentre phase II trial designed to evaluate the efficacy and safety of folinic acid, 5-fluorouracil and irinotecan (FOLFIRI) or capecitabine plus temozolomide (CAPTEM) regimens after failure of first-line chemotherapy in patients with lung NEC and GEP-NEC. EudraCT-2016-000767-17. Clinical Study Protocol Version 1, 7 November 2016.
Clinical • P2 data • Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
|
temozolomide • capecitabine • irinotecan • leucovorin calcium • fluorouracil topical
almost2years
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
IDH1 mutation • ATRX mutation
almost2years
[VIRTUAL] Serial ctDNA (circulating tumour DNA) for detection of genomic changes during neoadjuvant chemoradiotherapy (NACRT) in locally advanced rectal cancer (LARC) (ESMO 2020)
Funding: Northeast Cancer Research and Education Trust (NECRET), St Luke’s Institute of Cancer Research (SLICR) and the Ronnie Cox Award (Cancer Research Ireland). Clinical trial identification: NCT02151019 (CTRIAL-IE 12-38 TRI-LARC clinical trial).
Clinical
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FBXW7 (F-Box And WD Repeat Domain Containing 7) • SMAD4 (SMAD family member 4) • ATRX (ATRX Chromatin Remodeler)
|
BRAF V600E • KRAS mutation • NRAS mutation • BRAF V600 • PIK3CA mutation • ATRX mutation • EGFR mutation + KRAS mutation
almost2years
Clinical • P2 data • Journal
|
TP53 (Tumor protein P53) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • STK11 (Serine/threonine kinase 11) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ATRX (ATRX Chromatin Remodeler) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)
|
TP53 mutation • KIT mutation • ATRX mutation • PDGFRA mutation
|
dasatinib • imatinib • Sutent (sunitinib)
almost2years
Clinico-pathological and molecular characterization of diffuse midline gliomas: is there a prognostic significance? (PubMed, Neurol Sci)
The study highlights the differences in frequency and location of pediatric and adult DMGs. IHC (H-scoring) for H3K27M mutation is an excellent surrogate for sequencing. Prognosis remains dismal irrespective of age, location, and H3K27M status. Potential therapeutic targets need to be explored.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
almost2years
Genetic and epigenetic alterations in pancreatic neuroendocrine tumors. (PubMed, J Gastrointest Oncol)
Moreover, the dysregulated DNA methylation status is associated with distinct gene expression profiles. This article reviews the commonly and recently discovered genetic and epigenetic changes that are associated with PNETs, inherited PNETs, and genotype-phenotype associations, and it discusses their clinical relevance.
Review • Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • MTOR mutation
almost2years
Tumor mutational burden predicts survival in patients with low-grade gliomas expressing mutated IDH1. (PubMed, Neurooncol Adv)
Finally, we identified 6 gene sets that predict survival for LGG-mIDH-A and LGG-mIDH-O. we demonstrate that tumor mutational burden is a powerful, robust, and clinically relevant prognostic factor of MS in mIDH patients.
Clinical • Journal • Tumor Mutational Burden
|
TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • TMB-H • IDH1 mutation • TMB-L • ATRX mutation
almost2years
TP53, ATRX alterations, and low tumor mutation load feature IDH-wildtype giant cell glioblastoma despite exceptional ultra-mutated tumors. (PubMed, Neurooncol Adv)
gcGBMs have molecular features that contrast to "classic" IDHwt GBMs: unusually frequent ATRX mutations and few EGFR amplifications and CDKN2A deletions, especially in tumors with a high number of giant cells. TML is frequently low, although exceptional high TML suggests a potential for immune checkpoint therapy in some cases, which may be relevant for personalized medicine.
Journal • Tumor Mutational Burden
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • NF1 (Neurofibromin 1) • MSH2 (MutS Homolog 2) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • BRAF mutation • EGFR amplification • CDKN2A deletion • NF1 mutation • ATRX mutation • MSH2 mutation
almost2years
Spinal cord high-grade infiltrating gliomas in adults: clinico-pathological and molecular evaluation. (PubMed, Mod Pathol)
Median survival for cases with TP53 mutations was 11.5 months and for those with PPM1D mutations was 84 months. Our findings suggest that high-grade infiltrating gliomas of the spinal cord in adults represent a heterogeneous group of tumors, with variable outcomes possibly related to their molecular profiles.
Clinical • Journal
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • ATRX (ATRX Chromatin Remodeler) • PPM1D (Protein Phosphatase Mg2+/Mn2+ Dependent 1D)
|
TP53 mutation • BRAF V600E • BRAF V600 • ATRX mutation • IDH1 R132H • PPM1D mutation
almost2years
Biology and grading of pleomorphic xanthoastrocytoma-what have we learned about it? (PubMed, Brain Pathol)
Our data confirm the importance of WHO grading in histologically and epigenetically defined PXA. Methylation-based classification may be helpful in cases with ambiguous morphology, but is largely confirmatory in PXA with well-defined morphology.
Journal
|
BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ATRX (ATRX Chromatin Remodeler) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase)
|
TP53 mutation • BRAF V600E • BRAF V600 • CDKN2A deletion • ATRX mutation
almost2years
Identification of Prognostic Signatures of Alternative Splicing in Glioma. (PubMed, J Mol Neurosci)
In addition, these prognostic AS signatures could complement current molecular classification, such as IDH1 mutation, 1p/19q codeletion, and ATRX loss, of glioma and further identify potential subgroups of glioma with the same molecular features. In conclusion, our study systematically profiled prognostic AS events involving both low grade glioma and glioblastoma for the first time, which also shed light on the crosstalk between AS signatures and molecular features of glioma.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • MUTYH (MutY homolog)
|
IDH1 mutation • ATRX mutation
almost2years
Functional loss of ATRX and TERC activates Alternative Lengthening of Telomeres (ALT) in LAPC4 prostate cancer cells. (PubMed, Mol Cancer Res)
These LAPC-4 ATRXKO TERCmut cells continued to proliferate long-term and retained ALT-associated hallmarks, thereby demonstrating their reliance on the ALT mechanism for telomere maintenance. Implications: These prostate cancer cell line models provide a unique system to explore the distinct molecular alterations that occur upon induction of ALT, and may be useful tools to screen for ALT-specific therapies.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
almost2years
[VIRTUAL] The Spectrum of Genomic and Transcriptomic Alterations in ACTH-Producing and ACTH-Silent Corticotroph Adenomas (ENDO-I 2020)
Finally, C3 (n=6) contains a mixture of AS and CD cases (including CD without mutations in USP8) and features an expression profile that partly overlap with C1 tumors, but also exhibit higher expression of inflammatory genes. Taken together, our data suggest that CD and AS are distinct molecular subtypes of CA, highlighting the dominant role of USP8 mutations in driving a unique transcriptional program and illustrate for the first time that unlike most cases of CD, AS cases are characterized by profound genomic instability and cell cycle activation, features associated with a more aggressive disease course.
Late-breaking abstract
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler) • DAXX (Death-domain associated protein)
|
TP53 mutation • ATRX mutation
almost2years
[VIRTUAL] Analysis of ATRX and ZNRF3 Expression and Copy Number Variation in a Pediatric and Adult Cohort with Adrenocortical Tumors (ENDO-I 2020)
We confirmed the presence of alterations on ATRX and ZNRF3 genes in both cohort (adult and pediatric tumors). These results differ from the previous studies, which demonstrated ATRX and ZNRF3 alterations were present in pediatric and adult tumors, respectively. However, prospective studies with larger cohorts are necessary to confirm the prognostic value of ATRX and ZNRF3 genes in PAT and adults with ACC.
Clinical
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
almost2years
Pituitary Adenoma in Pediatric and Adolescent Populations. (PubMed, J Neuropathol Exp Neurol)
An elevated proliferation index of ≥3% and evidence of local invasion on imaging seem to correlate with a high probability of recurrence. Furthermore, we observe rarity of α-thalassemia/mental retardation syndrome X-linked (ATRX) protein loss (surrogate to ATRX mutation) in these tumors without any connotation on prognosis.
Clinical • Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
almost2years
FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma (clinicaltrials.gov)
P2, N=2, Terminated, University of Florida | N=100 --> 2 | Trial completion date: Apr 2024 --> Jun 2020 | Active, not recruiting --> Terminated | Trial primary completion date: Apr 2022 --> Jun 2020; The study was terminated because the Study Chair/IDE Sponsor and Novocure determined that conducting this trial was not feasible without CMS approval.
Clinical • Enrollment change • Trial completion date • Trial termination • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • TERT promoter mutation • TERT mutation
|
temozolomide
almost2years
Prognostic value of modified Glasgow prognostic score in recurrent high-grade glial tumors treated with systemic treatment. (PubMed, Clin Neurol Neurosurg)
In our study, mGPS was found to be an independent prognostic factor in patients with recurrent high-grade gliomas. If validated, mGPS can be used as an objective, easily calculated, cheap, and readily available prognostic model in routine practice.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler) • CRP (C-reactive protein)
|
ATRX mutation
almost2years
L1CAM High Expression Associates with Poor Prognosis in Glioma but Does Not Correlate with C11orf95-RELA Fusion. (PubMed, Biomed Res Int)
Although uncorrelated with C11orf95-RELA fusion, L1CAM was a significant poor prognostic marker in glioma patients. More aggressive treatment should be taken for these patients and L1CAM might be a promising therapeutic target in glioma.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
almost2years
Is Visible Aminolevulinic Acid-Induced Fluorescence an Independent Biomarker for Prognosis in Histologically Confirmed (World Health Organization 2016) Low-Grade Gliomas? (PubMed, Neurosurgery)
This is the first report investigating the role of ALA-induced fluorescence in histologically confirmed LGG. Fluorescence appeared to be a marker for inherent malignant transformation and OS, independently of known prognostic markers. Fluorescence in LGG might be taken into account when deciding on adjuvant therapies.
Journal
|
EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • EGFR expression • ATRX mutation
almost2years
Malignant Intrarenal/Renal Pelvis Paraganglioma with Co-Occurring SDHB and ATRX Mutations. (PubMed, Endocr Pathol)
Despite multiple surgical resections and various treatment modalities, the patient eventually elected for palliative care measures and died of disease. Together, the findings seen in this patient are unique and serve as an appropriate catalyst for discussing the unusual locations, interesting genetic profiles, and metastatic risk factors that may be associated with paragangliomas.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
almost2years
Genomic Molecular Classification of CNS Malignancies. (PubMed, Adv Anat Pathol)
Identification of novel gene fusions and matched DNA methylation signatures enable accurate diagnosis of primitive neuroectodermal tumors, which were previously misdiagnosed. Genomic classification of central nervous system tumors is being readily translated into the clinical practice and will enable molecularly based patient management and clinical trials.
Journal
|
TP53 (Tumor protein P53) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
almost2years
Synthetic lethality of cytolytic HSV-1 in cancer cells with ATRX and PML deficiency. (PubMed, J Cell Sci)
Sensitivity to mutant HSV-1 infection also correlated inversely with PML protein levels, and we showed that ATRX upregulates PML expression at both the transcriptional and post-transcriptional levels. These data provide a basis for predicting, based on ATRX or PML levels, which tumors will respond to a selective oncolytic herpesvirus.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
almost2years
MYCN amplification and ATRX mutations are incompatible in neuroblastoma. (PubMed, Nat Commun)
Therefore, ATRX and MYCN represent an unusual example, where inactivation of a tumor-suppressor gene and activation of an oncogene are incompatible. This synthetic lethality may eventually be exploited to improve outcomes for patients with high-risk neuroblastoma.
Journal
|
MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • ATRX (ATRX Chromatin Remodeler)
|
MYCN amplification • ATRX mutation
2years
[VIRTUAL] The differences in immune composition observed between astrocytomas and oligodendrogliomas are due to genetics (AACR-II 2020)
We conclude that the differences in immune composition between IDH-mutant glioma subtypes are due to genetics. In particular, ATRX loss of function in IDH-mutant astrocytoma leads to chromatin changes in STAT3 and downstream effector cytokines, resulting in a greater influx of immunosuppressive myeloid cells.
IO biomarker
|
ATRX (ATRX Chromatin Remodeler) • STAT3 (Signal Transducer And Activator Of Transcription 3) • CSF1 (Colony stimulating factor 1) • SOX2 • IL10 (Interleukin 10)
|
ATRX mutation
2years
[VIRTUAL] Potential molecular biomarkers of response to eribulin in patients with leiomyosarcoma (AACR-II 2020)
The recent randomized phase 3 trial Eisai Study 309 evaluated efficacy of eribulin (ERI) compared to dacarbazine (DTIC) in advanced liposarcoma (LPS) and leiomyosarcoma (LMS). We identified several molecular changes with potential impact on disease control and survival of LMS patients treated with ERI. These observations require further prospective validation.
Clinical
|
TP53 (Tumor protein P53) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
|
Halaven (eribulin mesylate) • dacarbazine
2years
[VIRTUAL] Translational and mechanistic implications of osteosarcoma genomics: A TARGET report (AACR-II 2020)
The TARGET OS data are publicly available (phs000218) and of immediate relevance to future investigations of the molecular mechanisms driving osteosarcoma. Findings suggest a path forward to improved assessment of risk for individual patients and support a precision medicine approach to future clinical trial development.
Late-breaking abstract
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • RB1 (RB Transcriptional Corepressor 1) • CCNE1 (Cyclin E1) • CDK4 (Cyclin-dependent kinase 4) • ATRX (ATRX Chromatin Remodeler) • IGF1R (Insulin-like growth factor 1 receptor)
|
TP53 mutation • PTEN mutation • MYC amplification • ATRX mutation
2years
Prognostic factors in progressive high-grade glial tumors treated with systemic approach: A single center experience. (PubMed, J Oncol Pharm Pract)
Our study is real life data and the median progression-free survival and overall survival rates are similar to the literature. We have found ECOG PS, presence of ATRX and IDH1 mutation to be independent prognostic factors for both progression-free survival and overall survival.
Clinical • Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
2years
Centromeric cohesion failure invokes a conserved choreography of chromosomal mis-segregations in pancreatic neuroendocrine tumor. (PubMed, Genome Med)
We propose an evolutionary model for a subset of aggressive PANETs that is initiated by mutation of MEN1, ATRX, and DAXX, resulting in defects in centromere cohesion from ectopic CENP-A deposition that leads to selective loss of chromosomes and the LOH phenotype seen in late-stage metastatic PANETs. These insights aid in disease risk stratification and nominate potential therapeutic vulnerabilities to treat this disease.
Journal
|
ATRX (ATRX Chromatin Remodeler) • CENPA (Centromere protein A)
|
ATRX mutation
2years
[VIRTUAL] The mutational pattern of homologous recombination (HR) related genes and its relevance to response to immunotherapy in gastric cancer. (ASCO 2020)
Our data suggests that detection of somatic mutations of HR-gene could expand the proportion of patients who might get benefit from immune checkpoint blockade therapy response. Research Funding: None
Tumor Mutational Burden • PD(L)-1 Biomarker • IO biomarker
|
MSI (Microsatellite instability) • HRD (Homologous Recombination Deficiency) • ATRX (ATRX Chromatin Remodeler) • ATR (Ataxia telangiectasia and Rad3-related protein)
|
PD-L1 expression • ATM mutation • HRD • ATRX mutation
2years
[VIRTUAL] Identification of genetic alterations in childhood and adolescence glioblastoma (GBM) using next generation sequencing strategy. (ASCO 2020)
Molecular profiling based on NGS genetic panel, specific for pediatric tumors, can provide information about potential prognostic biomarkers for GBM of childhood and adolescence. Thus, wider understanding about GBM biologic heterogeneity may lead to personalized therapeutic strategies for pediatric patients. Research Funding: Pediatric Oncology Institute/GRAACC., Other Government Agency.
Clinical • Next-generation sequencing
|
TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation
2years
[VIRTUAL] Genomic landscape of angiosarcoma: A targeted and immunotherapy biomarker analysis of 143 patients. (ASCO 2020)
Our findings suggest differential angiosarcoma biology across primary sites. HN AS had more frequent markers of potential IO-therapy response, as well as DDR alterations. Next in frequency, we found ARID1A which is possibly associated with overactive EZH2, a target of tazemetostat.
Clinical • Tumor Mutational Burden • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • ARID1A (AT-rich interaction domain 1A) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • ATRX (ATRX Chromatin Remodeler) • POT1 (Protection of telomeres 1)
|
TP53 mutation • MYC amplification • ARID1A mutation • ATRX mutation
|
Tazverik (tazemetostat)
2years
[VIRTUAL] Correlation of pathogenic POLE mutations with clinical benefit to immune checkpoint inhibitor therapy. (ASCO 2020)
Pathogenic POLE mutations were associated with clinical benefit to ICI therapy. Further studies are warranted to validate POLE mutations as a predictive biomarker. Multiple co-occurring DNA damage response mutations were found, which may contribute to ICI clinical benefit.
Clinical • Checkpoint inhibition • Tumor Mutational Burden • BRCA Biomarker • MSi-H Biomarker • PD(L)-1 Biomarker • IO biomarker
|
EGFR (Epidermal growth factor receptor) • BRAF (B-raf proto-oncogene) • KRAS (KRAS proto-oncogene GTPase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin-dependent kinase inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • POLE (DNA Polymerase Epsilon) • CDK12 (Cyclin dependent kinase 12) • ATRX (ATRX Chromatin Remodeler) • CREBBP (CREB binding protein) • ATR (Ataxia telangiectasia and Rad3-related protein)
|
KRAS mutation • BRCA2 mutation • ARID1A mutation • POLE mutation • ATRX mutation
2years
FORWARD Optune and Adjuvant TMZ in Grade II/III Astrocytoma (clinicaltrials.gov)
P2, N=100, Active, not recruiting, University of Florida | Recruiting --> Active, not recruiting
Clinical • Enrollment closed
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • TERT promoter mutation • TERT mutation
|
temozolomide
2years
Clinical applications of (epi)genetics in gastroenteropancreatic neuroendocrine neoplasms: Moving towards liquid biopsies. (PubMed, Rev Endocr Metab Disord)
Finally, we discuss recent studies on liquid biopsies in the field of GEP-NENs and illustrate how liquid biopsies can play a role in patient management. In conclusion, molecular studies have suggested multiple potential biomarkers, but further validation is ongoing.
Clinical • Review • Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
2years
1p/19q co-deleted fibrillary astrocytomas: Not everything that is co-deleted is an oligodendroglioma. (PubMed, Ann Diagn Pathol)
Only 1 of 11 of these cases also demonstrated evidence of an IDH mutation, potentially raising differential diagnostic confusion with oligodendroglioma. Use of LOH 1p/19q testing, if available, or other markers such as ATRX, p53 and EGFR may be helpful in avoiding misclassification of such tumors as oligodendroglioma.
Review • Journal
|
EGFR (Epidermal growth factor receptor) • IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • EGFR amplification • ATRX mutation
2years
Genomic Landscape of Uterine Sarcomas Defined through Prospective Clinical Sequencing. (PubMed, Clin Cancer Res)
Prospective genomic profiling can contribute to diagnostic precision and inform treatment selection in patients with uterine sarcomas. There was evidence of clinical benefit in uLMS patients with somatic BRCA2 alterations treated with PARP inhibitors.
Clinical • Journal • BRCA Biomarker • PARP Biomarker
|
TP53 (Tumor protein P53) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • ATRX (ATRX Chromatin Remodeler)
|
TP53 mutation • ATRX mutation • PTEN-H
2years
Immunohistochemistry for ATRX Can Miss ATRX Mutations: Lessons From Neuroblastoma. (PubMed, Am J Surg Pathol)
However, relaying on negative immunohistochemistry for ATRX protein to identify ALT in neuroblastoma may miss a significant proportion of patients. The addition of FISH for ALT as part of the diagnostic workup, especially for older children (5 y old and above), would help ensure that patients are correctly identified for anti-ALT therapy.
Journal
|
ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation
2years
Whole exome sequencing revealed mutational profiles of giant cell glioblastomas. (PubMed, Brain Pathol)
TERT promoter mutation and MGMT methylation were observed in 20% and 40% of our samples respectively. In conclusion, we described relevant mutation profiling for developing future targeted therapies in gcGBM.
Journal
|
TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • RB1 (RB Transcriptional Corepressor 1) • MSH6 (MutS homolog 6) • ATRX (ATRX Chromatin Remodeler)
|
PTEN mutation • ATRX mutation • MSH6 mutation
2years
Correlation of Molecular Markers in High Grade Gliomas with Response to Chemo-Radiation. (PubMed, Asian Pac J Cancer Prev)
Codeletion of 1p/19q with IDH1 mutation in HGG is associated with a significantly favourable PFS. However, larger studies with longer follow up are required to evaluate OS and PFS in all the molecular subgroups.
Journal
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1)
|
TP53 mutation • ATRX mutation
|
vincristine • lomustine
2years
Study of AG-120 and AG-881 in Subjects With Low Grade Glioma (clinicaltrials.gov)
P1, N=49, Active, not recruiting, Agios Pharmaceuticals, Inc. | Trial primary completion date: May 2024 --> Aug 2019
Clinical • Trial primary completion date
|
IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • ATRX (ATRX Chromatin Remodeler)
|
ATRX mutation • IDH1 R132H
|
Tibsovo (ivosidenib) • vorasidenib (AG-881)