News - CDKN2A deletion

ERBB2/ERBB3-mutated S100/SOX10-positive uterine sarcoma: something new. (PubMed, Virchows Arch)

The authors review the sparse literature on molecular-genetic aberrations involving the epidermal growth factor receptor family of receptor tyrosine kinases (ERBB1/EGFR, ERBB2, ERBB3, and ERBB4) in uterine mesenchymal tumors, a review that suggests that such tumors may be pathologically heterogeneous. The potential clinical significance of demonstrating a targetable ERBB2/ERBB3 tyrosine kinase mutation or other EGFR family aberrations, as well as its distinctive pathologic profile, supports the segregation of the tumor reported herein as a distinct and emerging entity.

6 days ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • PGR (Progesterone receptor) • FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ERBB3 (V-erb-b2 avian erythroblastic leukemia viral oncogene homolog 3) • NF1 (Neurofibromin 1) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • ATRX (ATRX Chromatin Remodeler) • ERBB4 (erb-b2 receptor tyrosine kinase 4) • CD34 (CD34 molecule) • NCAM1 (Neural cell adhesion molecule 1) • SOX10 (SRY-Box 10) • CD68 (CD68 Molecule) • MME (Membrane Metalloendopeptidase) • PRAME (Preferentially Expressed Antigen In Melanoma) • MLANA (Melan-A) • NTRK (Neurotrophic receptor tyrosine kinase) • PDGFB (Platelet Derived Growth Factor Subunit B) • STAT6 (Signal transducer and activator of transcription 6) • MITF (Melanocyte Inducing Transcription Factor)

EGFR mutation • HER-2 mutation • CDKN2A deletion • ATRX mutation • ERBB3 mutation • NF1 deletion

29d

Olıgosarcoma: A Rare Case Report Wıth Dıstınct Features. (PubMed, Int J Surg Pathol)

In our patient, the sarcomatous component exhibited p53 and OLIG2 immunohistochemical expression. Molecular analysis revealed IDH and TERT mutations, as well as 1p/19q and CDKN2A deletions.

29 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • OLIG2 (Oligodendrocyte Transcription Factor 2)

CDKN2A deletion • TERT mutation

A patient-derived xenograft mouse platform from epithelioid glioblastoma provides possible druggable screening and translational study. (PubMed, Am J Cancer Res)

By using the novel PDX platform, the results presented in this study demonstrate that the treatments with Palbociclib or Dabrafenib/Trametinib significantly reduced tumor size. In conclusion, PDX models offer a deeper understanding of eGBM at the genomic level and facilitate the identification of potential therapeutic targets. Further translational studies of this novel PDX model hold promise for advancing the diagnosis and treatment of this specific subtype of glioblastoma.

1 month ago

Preclinical • Journal

BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

BRAF V600E • BRAF V600 • CDKN2A deletion • CDKN2A mutation • CDKN2A mutation + BRAF V600E

Mekinist (trametinib) • Ibrance (palbociclib) • Tafinlar (dabrafenib)

Segmental CNV Detection with Oncomine Comprehensive Assay v3: Combined SNV and CNV Detection for Improved Glioma Diagnostics (AMP 2024)

Segmental CNV detection is feasible with the OCAv3 platform. Identified thresholds resulted in 100% sensitivity and specificity, although 20% to 30% of CDKN2A and +7/-10 cases require FISH reflex. If validated, this solution affords an efficient strategy in terms of hands-on-time, cost, and tissue use for combined SNV and CNV detection, particularly in a resource-constrained setting.

1 month ago

EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

EGFR amplification • CDKN2A deletion

Oncomine™ Comprehensive Assay v3M

CDKN2A homozygous deletion has stronger prognostic power than IDH mutation in CNS WHO grade 4 Gliomas. (SNO 2024)

The presenting study suggest that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcome due to CDKN2A deletion.

1 month ago

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion • CDKN2A mutation • IDH wild-type

OncoaccuPanel™

CD19-CAR T Cells As Definitive Consolidation for Older Adults with B-Cell Acute Lymphoblastic Leukemia in First Complete Remission: A Pilot Study (ASH 2024)

Ten (77%) pts received blinatumomab as part of initial therapy...Among pts who completed the DLT period (n=11), 7 (64%) experienced transient grade (G) 1 cytokine release syndrome (CRS) that resolved with tocilizumab +/- corticosteroid...CAR T cells had a robust expansion in the blood and CSF despite the low antigen setting. We have observed preliminary durable remissions and pts maintained function and cognition on day 100 post CAR-T.

1 month ago

Clinical • CAR T-Cell Therapy

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KMT2A (Lysine Methyltransferase 2A) • EP300 (E1A binding protein p300) • TCF3 (Transcription Factor 3) • PBX1 (PBX Homeobox 1) • ZNF384 (Zinc Finger Protein 384)

CDKN2A deletion

clonoSEQ

Blincyto (blinatumomab) • Actemra IV (tocilizumab)

2ms

Prevalence and co-mutation status of MTAP deletions (COSA 2024)

MTAP deletions are common in the MoST/CaSP population, most frequently in CNS, pancreas, lung and melanoma patients. Detection of MTAP deletion was higher with the FM1&A paltform. MTAP deletions co-existed with CDKN2A deletions in >80% of the cohort.

2 months ago

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)

CDKN2A deletion • MTAP deletion • KRAS deletion

TruSight Oncology 500 Assay

2ms

CDKN2A Homozygous Deletion Is a Stronger Predictor of Outcome than IDH1/2-Mutation in CNS WHO Grade 4 Gliomas. (PubMed, Biomedicines)

The present study suggests that CDKN2A deletion plays a powerful prognostic role in CNS WHO grade 4 gliomas. Even if CNS WHO grade 4 gliomas have mutant IDH1/2, they may have poor clinical outcomes because of CDKN2A deletion.

2 months ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase)

IDH1 mutation • CDKN2A deletion • CDKN2A mutation • MGMT promoter methylation • IDH wild-type

OncoaccuPanel™

2ms

BRAF/MEK inhibitors use for pediatric gliomas; real world experience from a resource-limited country. (PubMed, Front Oncol)

Two patients with BRAFv600E-mutated/CDKN2A deleted PXA-2, had progression following resection, and experienced stable/partial response at 9 months of dabrafenib use...Two patients who stopped trametinib due to side effects (significant acneiform rash/paronychia and intracranial bleeding) did not experience progression. Our experience with BRAF/MEK inhibitors' use was positive achieving response in all LGGs and provided sustained response with good quality of life for patients with HGG. Cost effectiveness analyses and patients' satisfaction comparisons with chemotherapy are needed to evaluate the routine use of these drugs in LMICs.

2 months ago

Journal • Real-world evidence • Real-world

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FGFR (Fibroblast Growth Factor Receptor)

BRAF V600E • FGFR mutation • CDKN2A deletion • CDKN2A mutation • BRAF fusion

Mekinist (trametinib) • Tafinlar (dabrafenib)

2ms

High-Grade Progression, Sarcomatous Transformation, and/or Metastasis of Pituitary Neuroendocrine Neoplasms (PitNENs): The UCSF Experience. (PubMed, Endocr Pathol)

We conclude that metastatic PitNET is not the only high-grade form of pituitary NEN. If further confirmed, these histopathologic and/or molecular features could provide advanced warning of biological aggressiveness and be applied towards a future grading scheme.

2 months ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • PDGFRB (Platelet Derived Growth Factor Receptor Beta) • ATRX (ATRX Chromatin Remodeler)

TP53 mutation • PIK3CA mutation • PTEN mutation • CDKN2A deletion • TP53 expression • PDGFRB mutation

3ms

Molecular pathogenesis of adult T-cell leukemia/lymphoma (PubMed, Rinsho Ketsueki)

Here we summarize the current understanding of the molecular pathogenesis of ATLL, focusing on recent progress made by genetic, epigenetic, and single-cell analyses. These findings not only provide a deeper understanding of the molecular pathobiology of ATLL, but also have significant implications for diagnostic and therapeutic strategies.

3 months ago

Review • Journal • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IRF4 (Interferon regulatory factor 4) • PRKCB (Protein Kinase C Beta)

CDKN2A deletion • PD-L1 amplification • IRF4 mutation • PD-L1 mutation

3ms

MTAP protein status is highly concordant with CDKN2A fluorescent in situ hybridization and allows stratification of the luminal subtype in muscle-invasive bladder cancer. (PubMed, Histopathology)

Our findings highlight CDKN2A HD and MTAP loss as prevalent genetic alterations in MIBC and mUC, particularly within the luminal-URO subtype and FGFR3-mutated, p53-normal/wildtype tumours. MTAP IHC can serve as a surrogate marker for 9p21.3 HD, highlighting its clinical relevance and potential as a therapeutic target and predictive biomarker in MIBC.

3 months ago

Journal • Discordant

TP53 (Tumor protein P53) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)

TP53 mutation • TP53 wild-type • FGFR3 mutation • CDKN2A deletion • CDKN2A deletion + MTAP deletion

3ms

AB003. Clinical analysis of central nervous system (CNS) World Health Organization (WHO) grade 4 gliomas with IDH-mutant versus IDH-wildtype focused on CDKN2A homozygous deletion. (PubMed, Chin Clin Oncol)

The presenting study suggests that CDKN2A deletion should play a powerful prognostic role in CNS WHO grade 4 gliomas as well as low-grade glioma. Even if CNS WHO grade 4 gliomas had mutant IDH, they can have poor clinical outcomes due to CDKN2A deletion.

3 months ago

Retrospective data • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase)

CDKN2A deletion • CDKN2A mutation • MGMT promoter methylation • IDH wild-type

3ms

First-in-human study of AMG 193, an MTA-cooperative PRMT5 inhibitor, in patients with MTAP-deleted solid tumors: results from phase 1 dose exploration. (PubMed, Ann Oncol)

AMG 193 demonstrated a favorable safety profile without clinically significant myelosuppression. Encouraging antitumor activity across a variety of MTAP-deleted solid tumors was observed based on ORR and ctDNA clearance.

3 months ago

P1 data • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)

CDKN2A deletion • MTAP deletion

AMG 193

7ms

Allogeneic haematopoietic stem cell transplantation might overcome the poor prognosis of adolescents and adult patients with T-lineage acute lymphoblastic leukaemia and CDKN2 deletion. (PubMed, Bone Marrow Transplant)

And multivariate analysis confirmed the beneficial role of allo-HSCT in OS (HR 0.23, P < 0.001). In conclusion, CDKN2 deletion was associated with a poor prognosis in adult T-ALL, and allo-HSCT might be beneficial for this population.

7 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

7ms

Differential expression of DMD transcripts as a novel prognostic biomarker in histologically diverse mesotheliomas. (PubMed, Transl Lung Cancer Res)

Further studies are needed to understand the role of specific dystrophin transcripts in cancer and TME cells, and their implications in the pathogenesis and progression of mesothelioma. Identifying patients at risk of poor survival based on DMD transcript expression can guide treatment strategies in mesothelioma, informing decisions regarding treatment intensity, follow-up schedules, eligibility for clinical trials, and ultimately, end-of-life care planning.

7 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

7ms

CDKN2A/B homozygous deletion sensitizes IDH-mutant glioma to CDK4/6 inhibition. (PubMed, Clin Cancer Res)

IDH-mutant gliomas with deletion of CDKN2A/B are sensitized to CDK4/6 inhibitors. These results support investigation of the use of these agents in a clinical setting.

7 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • CDK4 mutation

Ibrance (palbociclib) • Verzenio (abemaciclib)

8ms

P16-CD8-Ki67 Triple Algorithm for Prediction of CDKN2A Mutations in Patients with Multiple Primary and Familial Melanoma. (PubMed, Diagnostics (Basel))

In conclusion, p16, CD8, and Ki67 individually serve as valuable indicators for predicting melanoma evolution. The algorithm, comprising these three immunohistochemical parameters based on their prognostic and evolutionary significance, proves to be a valuable auxiliary diagnostic tool for cost-effective prediction of mutational status in detecting multiple and familial primary melanomas with CDKN2A homozygous deletion.

8 months ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8)

TP53 mutation • CDKN2A deletion • CDKN2A mutation • TP53 expression

8ms

Loss of p16 Immunoexpression and Deletions of CDKN2A in the Progression of Extramammary Paget Disease: An Immunohistochemical and Genetic Study of 24 Invasive/Metastatic Cases. (PubMed, Am J Dermatopathol)

CDKN2A homozygous deletions were confirmed in all 5 tested cases by sequencing, whereas MTAP deletions were detected in only 2 cases. In conclusion, p16 expression loss and CDKN2A deletions can be frequently seen in invasive/metastatic cases of EMPD.

8 months ago

Journal • Metastases

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)

CDKN2A deletion • MTAP deletion

8ms

Uterine Inflammatory Myofibroblastic Tumors: p16 as a Surrogate for CDKN2A Deletion and Predictor of Aggressive Behavior. (PubMed, Am J Surg Pathol)

Thus, we recommend performing p16 on all uterine IMTs, which, combined with the risk stratification score, is a promising and cost-effective tool for predicting CDKN2A status and outcome in these patients. It may be particularly useful for tumors with incomplete information for risk stratification (ie, morcellated tumors) and for further stratifying intermediate-risk IMTs when sequencing is unavailable.

8 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase)

CDKN2A deletion • TERT mutation • TERT promoter mutation

8ms

Intratumoral heterogeneity of CDKN2A deletions in IDH-mutant astrocytoma. (PubMed, Brain Tumor Pathol)

No abstract available

8 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion • CDKN2A mutation

9ms

Reliably making the primary diagnosis of mesothelioma utilizing serous fluid cytology specimens: an institutional experience. (PubMed, J Am Soc Cytopathol)

The diagnosis of mesothelioma can be reliably made on SFC with the appropriate cytomorphology criteria and/or confirmatory ancillary testing.

9 months ago

Journal • Cytology

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BAP1 (BRCA1 Associated Protein 1)

CDKN2A deletion

9ms

Landscape of driver mutations and their clinical effects on Down syndrome-related myeloid neoplasms. (PubMed, Blood)

Patients with CDKN2A deletions (n = 7) or TP53 mutations (n = 4) had substantially lower 3-year event-free survival [28.6% vs. 90.5%, P < 0.001; 25.0% vs. 89.5%, P < 0.001] than those without these mutations. These findings considerably change the mutational landscape of ML-DS, provide new insights into the mechanisms of progression from TAM to ML-DS, and help identify new therapeutic targets and strategies for ML-DS.

9 months ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • JAK2 (Janus kinase 2) • RUNX1 (RUNX Family Transcription Factor 1) • ZBTB7A (Zinc finger and BTB domain containing 7A)

TP53 mutation • CDKN2A deletion

10ms

Somatic CDKN2A copy number variations are associated with the prognosis of esophageal squamous cell dysplasia. (PubMed, Chin Med J (Engl))

The results indicated that CDKN2A SCNVs are associated with the prognosis of ESCdys and may serve as potential biomarkers for risk stratification.

10 months ago

Clinical • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

10ms

Longitudinal analyses of clinical sequencing data provide novel insights into the evolutionary dynamics of lung adenocarcinoma (AACR 2024)

In LUAD, metastatic specimens exhibit increased chromosomal instability in relation to their matched primaries. This translates into unique copy number alterations detected only in the metastasis. By contrast, driver mutations - which account for most of the clinically targetable alterations with currently approved FDA drugs - are more often shared between paired samples from the same patient.

10 months ago

Clinical • Tumor mutational burden

EGFR (Epidermal growth factor receptor) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

MET amplification • CDKN2A deletion

MSK-IMPACT

11ms

Investigation of MTAP and BAP1 staining loss and P16/CDKN2A deletion in pleural cytology specimens and its role in the diagnosis of mesothelioma. (PubMed, Diagn Cytopathol)

It has been determined that any marker alone cannot be used for a definitive mesothelioma diagnosis in pleural effusion cytological specimens; however, sensitivity increases in some combinations. The combination of BAP1 immunohistochemistry and p16/CDKN2A homozygous deletion detected by FISH, which has a higher specificity and sensitivity, can be routinely used in the diagnosis of mesothelioma under the guidance of clinical and radiologic information.

11 months ago

Journal • Cytology

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1)

CDKN2A deletion

11ms

Improved prognostic stratification of patients with isocitrate dehydrogenase-mutant astrocytoma. (PubMed, Acta Neuropathol)

Combination of these parameters allows for improved prediction of outcome. These data aid in designing upcoming trials using IDH inhibitors.

11 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MGMT (6-O-methylguanine-DNA methyltransferase)

CDKN2A deletion • MGMT promoter methylation

12ms

Spitz Tumors and Melanoma in the Genomic Age: A Retrospective Look at Ackerman's Conundrum. (PubMed, Cancers (Basel))

A ternary classification Spitz nevus-Spitz melanocytoma-Spitz melanoma is more adherent to the real neoplastic pathway, but some cases with intermediate ambiguous features remain difficult to diagnose. A prognostic stratification of Spitz tumors, based on the morphologic and genomic characteristics, as a complement to the diagnosis, may contribute to better treatment plans for patients.

12 months ago

Retrospective data • Review • Journal

BRAF (B-raf proto-oncogene) • ALK (Anaplastic lymphoma kinase) • ROS1 (Proto-Oncogene Tyrosine-Protein Kinase ROS) • NTRK1 (Neurotrophic tyrosine kinase, receptor, type 1) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • MAP3K8 (Mitogen-Activated Protein Kinase Kinase Kinase 8)

BRAF mutation • NTRK1 fusion • NTRK2 fusion • ALK fusion • CDKN2A deletion • HRAS mutation • TERT mutation

1year

FISH analysis reveals CDKN2A and IFNA14 co-deletion is heterogeneous and is a prominent feature of glioblastoma. (PubMed, Brain Tumor Pathol)

Furthermore, wt (intact) CDKN2A/IFNA14 were found to be associated with longer survival in recurrent GBMs. Our data suggest that co-deletion of CDKN2A/IFNA14 in GBM negatively correlates with survival and CDKN2A-wt status correlated with longer survival, and with second surgery, itself a marker for improved patient outcomes.

1 year ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion • CDKN2A negative

1year

Sarcomatoid mesothelioma diagnosed in a patient with mesothelioma in situ: a case report on morphologic differences after 9-month interval with details analysis of cytology in early-stage mesothelioma. (PubMed, Diagn Pathol)

Our case suggests that cell-in-cell engulfment can be conspicuous in early-stage mesothelioma with inconspicuous nuclear atypia and few multinucleated cells. In addition, the presence of MTAP loss and CDKN2A homozygous deletion are suspected to be involved in early formation to invasive lesions and/or sarcomatoid morphology. We believe that it is important to consider genetic abnormalities when deciding on individual patient management. Furthermore, cases of mesothelioma, even those of an in situ lesion, with MTAP loss and/or CDKN2A deletion should be carefully followed up or subjected to early treatment.

1 year ago

Journal • Cytology

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase)

CDKN2A deletion

1year

Molecular profiles of different PD-L1 expression in patients with esophageal squamous cell carcinoma. (PubMed, Cancer Biol Ther)

In this study, we presented the prevalence rates of PD-L1 expression in Chinese ESCC patients. The association of genetic profiles with PD-L1 expression levels also provide the clue that genomic phenotype may interact with the immunologic phenotype in ESCC.

1 year ago

Journal • BRCA Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • BRCA1 (Breast cancer 1, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CD8 (cluster of differentiation 8) • CD68 (CD68 Molecule) • TGFB1 (Transforming Growth Factor Beta 1)

PD-L1 expression • PD-L1 overexpression • NF1 mutation • CDKN2A deletion • PD-L1-L

1year

Massive parallel sequencing unveils homologous recombination deficiency in follicular dendritic cell sarcoma. (PubMed, Haematologica)

Absence of mutations in the RAS/RAF/MAPK pathway and lack of clonal hematopoiesis related mutations in FDCS sanction its differences from dendritic cell-derived neoplasms of haematopoietic derivation. WGS and WES in FDCS provides additional information on the molecular landscape of this rare tumor, proposing novel candidate genes for innovative therapeutical approaches to improve survival of patients with multifocal disease.

1 year ago

Journal • Tumor mutational burden • BRCA Biomarker • PARP Biomarker • PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TMB (Tumor Mutational Burden) • BRCA2 (Breast cancer 2, early onset) • HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1)

PD-L1 expression • HRD • TMB-L • RAS mutation • CDKN2A deletion

1year

Genomic characterization of IDH-mutant astrocytoma progression to grade 4 in the treatment setting. (PubMed, Acta Neuropathol Commun)

All patients in our discovery cohort received radiation, all but one underwent chemotherapy, and no patient received temozolomide (TMZ) before progression to grade 4 disease...In our retrospective analysis of patient treatment and survival timelines (n = 75), the combination of postoperative radiation and chemotherapy (mainly TMZ) outperformed radiation, especially in the grade 3 tumor cohort, in which it was typically given after primary surgery. Our results provide further insight into the contribution of treatment and genetic alterations in cell cycle, growth factor signaling, and DNA repair-related genes to tumor evolution and progression.

1 year ago

Journal

MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • DNMT3A (DNA methyltransferase 1) • RB1 (RB Transcriptional Corepressor 1) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • MSH2 (MutS Homolog 2) • RAD51B (RAD51 Paralog B) • NRG3 (Neuregulin 3)

CDKN2A deletion • MSH2 mutation • NRG3 deletion

temozolomide

1year

Linear grading coefficient reveals embryonic development gene signature as treatment-independent prognostic factor in IDH-mutant astrocytoma (SNO 2023)

Our study highlights upregulation of embryonic development genes as potential molecular mechanism associated with malignancy of IDH-mutant astrocytomas.

1 year ago

Gene Signature

CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion

1year

Genetic and epigenetic profiling of meningiomas to gain insights into molecular heterogeneity and risk stratification. (SNO 2023)

Genome-wide DNA methylation profiling reveals clinically distinct molecular subgroups and heterogeneity within the same grade of meningiomas and is particularly valuable for identifying high-risk cases and predicting prognosis in WHO grade 1 and 2 meningiomas. The pTERT mutation serves as a significant and cost-effective marker for risk stratification in meningiomas.

1 year ago

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • TERT (Telomerase Reverse Transcriptase)

CDKN2A deletion • CDKN2A mutation • TERT mutation

1year

A multi-center, progression-free survival analysis in IDH-mutant gliomas with CDKN2A deletion: Implications for prognosis and clinical trial design. (SNO 2023)

Notably, however, PFS for the grade 4, CDKN2A-intact, IDH-mutant glioma comparison group is estimated at 5.9 years (95% CI 3.3 – 7.9 years). Overall, these data reinforce the accelerated disease course associated with deletion of CDKN2A in IDH-mutant gliomas, providing an important reference for clinical trial design.

1 year ago

Clinical

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion • CDKN2A mutation

1year

Development of combination therapies of KRASG12C inhibitor adagrasib in preclinical models of brain metastasis (SNO 2023)

MRTX849 combination therapies with abemaciclib or anti-PD-1 demonstrate intracranial activity, inhibiting BM progression and prolonging survival, in preclinical models of KRASG12C+ BM.

1 year ago

Preclinical • Combination therapy • PD(L)-1 Biomarker • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • KRAS deletion

Verzenio (abemaciclib) • Krazati (adagrasib)

1year

Molecular diagnostics for vitreoretinal lymphoma (PubMed, Pathologie (Heidelb))

PVRL, as well as secondary vitreoretinal lymphomas after PCNSL or extracerebral DLBCL, have high mutation frequencies in characteristically mutated genes in PCNSL or MCD/cluster 5 type DLBCL. Supporting diagnostics, mutation detection can also be performed on cell-free DNA from the vitreous supernatant.

1 year ago

Review • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD79B (CD79b Molecule) • CD79A (CD79a Molecule)

CDKN2A deletion • CDKN2A mutation • CD79B mutation • CD79B mutation • CD79A mutation • CD79A mutation + CD79B mutation

1year

p16 Immunohistochemistry as a Screening Tool for Homozygous CDKN2A Deletions in CNS Tumors. (PubMed, Am J Surg Pathol)

Immunohistochemistry for p16 proved to have a high positive predictive value (range 90% to 100%) and an overall low negative predictive value (range 22% to 93%) for a homozygous CDKN2A deletion. In a setting where molecular testing is limited for cost and time reasons, p16 immunohistochemistry serves as a useful and rapid screening tool for identifying cases that should be subjected to further molecular testing for CDKN2A deletions.

1 year ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RELA (RELA Proto-Oncogene) • ZFTA (Zinc Finger Translocation Associated)

CDKN2A deletion • IDH wild-type

1year

Successes and challenges in modeling heterogeneous BRAF mutated central nervous system neoplasms. (PubMed, Front Oncol)

We discuss which research gaps each model might be best suited to answer, and identify those areas in model development that need to be strengthened further. We highlight areas of potential research focus that will lead to the heightened predictive capacity of preclinical studies, allow for appropriate validation, and ultimately improve the success of "bench to bedside" translational research.

1 year ago

Review • Journal

BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

BRAF mutation • CDKN2A deletion • CDKN2A mutation