News - CDKN2A deletion

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 day ago

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

EGFR amplification • CDKN2A deletion

Oncomine™ Comprehensive Assay v3M

11d

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.

11 days 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

15d

Ganglioglioma with MAP2K1 Mutation and CDKN2A/B Homozygous Deletion: A Case Report. (PubMed, Br J Hosp Med (Lond))

Subsequently, salvage chemotherapy with a combination of temozolomide and irinotecan was administered, resulting in effective control of the tumor. Conclusion To our knowledge, this is the first reported case of ganglioglioma with anaplastic features harboring MAP2K1 mutation and homozygous deletion of CDKN2A/B. These findings may shed light on the genetic features of ganglioglioma and offers insights into potential therapeutic approaches for this rare neoplasm.

15 days ago

Journal

BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

BRAF V600E • BRAF V600 • CDKN2A deletion • CDKN2A mutation

temozolomide • irinotecan

15d

Soft Tissue Tumor with PAK2::RAF1 Kinase Fusion: An Emerging Sarcoma Entity. (PubMed, Case Rep Oncol)

There was no evidence of disease progression at 4 months. This is the first case of a soft tissue tumor harboring a PAK2::RAF1 fusion with histological features in keeping with previous cases of RAF1 and other kinase fusion soft tissue tumors.

15 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • CD34 (CD34 molecule) • PAK2 (P21 (RAC1) Activated Kinase 2)

CDKN2A deletion

16d

The molecular history of IDH-mutant astrocytomas without adjuvant treatment. (PubMed, Brain Pathol)

In summary, our studies demonstrated, in contrast to the phenomenon of temozolomide-induced hypermutation, IDH-mutant, 1p19q non-codeleted Grade 2 astrocytomas which had not been treated by temozolomide, acquired new CNVs at tumor recurrences. These findings improve our understanding of the molecular life history of IDH-mutant astrocytomas.

16 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha)

CDKN2A deletion

temozolomide

19d

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.

19 days 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™

19d

Dual phenotypes in recurrent astrocytoma, IDH-mutant; coexistence of IDH-mutant and IDH-wildtype components: a case report with genetic and epigenetic analysis. (PubMed, Acta Neuropathol Commun)

Because these genetic abnormalities can drive oncogenic pathways, such as the PI3K/AKT/mTOR and RB signaling pathway, IDH-mutant gliomas that acquired these mutations were no longer dependent on the initial driver mutation, the IDH mutation. Molecular analysis of this unique case provides insight that in a subset of astrocytoma, IDH-mutant that acquired these genetic abnormalities, IDH mutation may not play a pivotal role in tumor growth and acquisition of these genetic abnormalities may contribute to the acquisition of resistance to IDH inhibitors.

19 days ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • IDH wild-type

22d

Frequency and Prognostic Impact of CDKN2A/B Alteration in Oligodendrogliomas: Systematic Review and Meta-analysis. (PubMed, Neurol Med Chir (Tokyo))

The frequency (95% CI) of other alterations of the CDKN2A/B gene, i.e., mutation, hemizygous deletion, and promoter methylation, was estimated as 1.48% (0.6-3.5), 15.9% (9.8-24.7), and 20.6% (13.7-29.8), respectively. The clinical significance of these alterations remains unclear due to the immaturity of the investigations.

22 days ago

Retrospective data • Review • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDK2 (Cyclin-dependent kinase 2)

CDKN2A deletion • CDKN2A mutation

24d

Mutational landscape of Japanese patients with oral squamous cell carcinoma from comprehensive genomic profiling tests. (PubMed, Oral Oncol)

This study analyzed the genomic profiles of patients with OSCC in Japan and the genetic differences between OSCC and other HNSCC subtypes. This analysis offers insights into the development of personalized therapeutics for OSCC.

24 days ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CASP8 (Caspase 8)

CDKN2A deletion

24d

Reappraisal of prognostic factors in CNS WHO grade 3 oligodendrogliomas IDH-mutant and 1p/19q co-deleted: lessons from the French POLA cohort. (PubMed, Neuro Oncol)

Necrosis and CDKN2A HD are adverse prognostic factors of WHO grade 3 oligodendrogliomas, IDH mutant and 1p/19q co-deleted. Besides, in group 1 patients, lack of contrast enhancement is a factor of better prognosis.

24 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MVP (Major Vault Protein)

CDKN2A deletion

24d

A multi-center, clinical analysis of IDH-mutant gliomas, WHO Grade 4: implications for prognosis and clinical trial design. (PubMed, J Neurooncol)

These findings underscore the severe prognostic impact of CDKN2A/B deletion in IDH-mutant astrocytomas and highlight the need for further refinement of tumor prognostic categorization. Our results provide a key benchmark of baseline patient outcomes for therapeutic trials, underscoring the importance of CDKN2A/B status assessment, in addition to histologic grading, in clinical trial design and therapeutic decision-making for IDH-mutant astrocytoma patients.

24 days ago

Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • CDKN2A mutation • IDH wild-type

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.

1 month 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)

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.

1 month 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

Uterine mesenchymal tumours harboring the KAT6B/A::KANSL1 gene fusion represent a distinct type of uterine sarcoma based on DNA methylation profiles. (PubMed, Virchows Arch)

In conclusion, KAT6B/A::KANSL1 uterine sarcoma is a molecularly unique type of uterine tumour that should be recognized as a distinct entity. These tumors typically exhibit low-grade histologic features but are occasionally morphologically high-grade; the latter have a DNA methylation profile different from the typical low-grade neoplasms and may be associated with aggressive behaviour.

1 month ago

Journal • Epigenetic controller

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • KAT6B (Lysine Acetyltransferase 6B)

CDKN2A deletion

Epigenetic landscape reorganisation and reactivation of embryonic development genes are associated with malignancy in IDH-mutant astrocytoma. (PubMed, Acta Neuropathol)

RNA-sequencing was conducted on primary IDH-mutant astrocytomas (n = 138) included in the prospective CATNON trial, which was performed to assess the prognostic effect of adjuvant and concurrent temozolomide...Higher grade IDH-mutant astrocytomas have DNA-methylation signatures that, on the RNA level, are associated with increased cell cycling, tumour cell de-differentiation and extracellular matrix remodelling. These combined molecular signatures can serve as an objective marker for grading of IDH-mutant astrocytomas.

1 month ago

Journal

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

CDKN2A deletion

temozolomide

Testicular large B-cell lymphoma is genetically similar to PCNSL and distinct from nodal DLBCL. (PubMed, Hemasphere)

However, we observed a subgroup of patients classified as BN2, both in localized and disseminated TLBCL, suggesting a degree of genetic heterogeneity in the TLBCL genetic profile. TLBCL has a distinctive genetic profile similar to PCNSL, supporting its recognition as a separate entity from DLBCL and might provide information to devise targeted therapeutic approaches.

1 month ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • BCL6 (B-cell CLL/lymphoma 6) • ETV6 (ETS Variant Transcription Factor 6) • CD79B (CD79b Molecule) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • EP300 (E1A binding protein p300) • PIM1 (Pim-1 Proto-Oncogene) • NODAL (Nodal Growth Differentiation Factor) • TBL1XR1 (TBL1X Receptor 1)

CDKN2A deletion • MYD88 L265P • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement • ETV6 mutation

Recurrent symptomatic intracranial hemorrhage in high-grade astrocytoma with piloid features: illustrative case. (PubMed, J Neurosurg Case Lessons)

Although recurrent symptomatic intracranial hemorrhages are rare in HGAP, enhancing lesions on magnetic resonance imaging suggest the need for resection to obtain tissue for molecular diagnosis and guide adjuvant treatment strategies. https://thejns.org/doi/10.3171/CASE24395.

1 month ago

Journal

FGFR1 (Fibroblast growth factor receptor 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase) • TACC1 (Transforming Acidic Coiled-Coil Containing Protein 1)

CDKN2A deletion • FGFR1 fusion • FGFR1-TACC1 fusion

A clinically feasible algorithm for the parallel detection of glioma-associated copy number variation markers based on shallow whole genome sequencing. (PubMed, J Pathol Clin Res)

Furthermore, we applied the algorithm to an independent glioma cohort and observed the expected sample distribution and prognostic stratification patterns. In conclusion, we provide a clinically applicable algorithm to classify the CNV status of glioma-associated markers in parallel.

1 month ago

Journal

EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

EGFR amplification • CDKN2A deletion

-New frontiers in domain-inspired radiomics and radiogenomics: increasing role of molecular diagnostics in CNS tumor classification and grading following WHO CNS-5 updates. (PubMed, Cancer Imaging)

In this review, we explore the relative benefits and drawbacks of these computational frameworks and highlight the technical and clinical innovations presented by recent studies in the landscape of fast evolving molecular-based Glioma subtyping. Furthermore, the potential benefits and challenges of incorporating these tools into routine radiological workflows, aiming to enhance patient care and optimize clinical outcomes in the evolving field of CNS tumor management, have been highlighted.

1 month ago

Review • Journal

EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

EGFR mutation • EGFR amplification • CDKN2A deletion • TERT mutation • TERT promoter mutation

Re-irradiation of anaplastic meningioma: higher dose and concomitant Bevacizumab may improve progression-free survival. (PubMed, Radiat Oncol)

Re-irradiation presents a viable option for recurrent anaplastic meningioma despite the associated risk of radiation necrosis. Higher doses with concomitant Bevacizumab improve clinical outcomes and reduce toxicity. Individualized treatment approaches are necessary, emphasizing the importance of further research to refine management strategies for this challenging disease.

1 month ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

Avastin (bevacizumab)

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.

1 month 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

Survival Outcomes Associated With First-Line Procarbazine, CCNU, and Vincristine or Temozolomide in Combination With Radiotherapy in IDH-Mutant 1p/19q-Codeleted Grade 3 Oligodendroglioma. (PubMed, J Clin Oncol)

In patients with newly diagnosed O3IDHmt/Codel from the POLA cohort, first-line PCV/RT was associated with better OS outcomes compared with TMZ/RT. Our data suggest that the improved safety profile associated with TMZ comes at the cost of inferior efficacy in this population. Further investigation using prospective randomized studies is warranted.

1 month ago

Journal • Combination therapy

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

temozolomide • vincristine • Matulane (procarbazine hydrochloride)

2ms

Epithelioid Fibrous Histiocytoma Is on a Continuum With Superficial ALK-rearranged Myxoid Spindle Cell Neoplasm: A Clinicopathologic Series of 35 Cases Including Alternate RET and NTRK3 Fusions. (PubMed, Am J Surg Pathol)

SAMS is on a morphologic and molecular genetic spectrum with EFH, with a similar body site distribution, frequent clinical presentation as an exophytic skin tumor, and invariably benign outcomes; we conclude that SAMS should be considered a histologic variant of EFH. Some morphologically typical examples harbor alternate RET and NTRK3 fusions, such that SAMS is not an appropriate designation for this morphologic class; instead, to highlight the clinicopathologic similarities to EFH, we propose the diagnostic term "myxoid spindle cell variant of epithelioid fibrous histiocytoma."

2 months ago

Journal

ALK (Anaplastic lymphoma kinase) • RET (Ret Proto-Oncogene) • NTRK3 (Neurotrophic tyrosine kinase, receptor, type 3) • EML4 (EMAP Like 4) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CD34 (CD34 molecule) • NCOA4 (Nuclear Receptor Coactivator 4) • DCTN1 (Dynactin Subunit 1) • SQSTM1 (Sequestosome 1) • MPRIP (Myosin Phosphatase Rho Interacting Protein) • SPECC1L (Sperm Antigen With Calponin Homology And Coiled-Coil Domains 1 Like) • PLEKHH2 (Pleckstrin Homology, MyTH4 And FERM Domain Containing H2) • PRKAR1A (Protein Kinase CAMP-Dependent Type I Regulatory Subunit Alpha)

NTRK3 fusion • RET fusion • ALK rearrangement • ALK fusion • CDKN2A deletion • NCOA4-RET fusion

2ms

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.

2 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

2ms

Comparative analysis of PD-L1 expression and molecular alterations in primary versus metastatic lung adenocarcinoma: a real-world study in China. (PubMed, Front Oncol)

Samples of metastatic tumors exhibited a higher proportion of elevated PD-L1 expression, a greater number of pathway alterations, and a higher occurrence of CDKN2A copy number deletions than primary samples. This highlights the importance of reinforcing the clinical management and follow-up of patients with CDKN2A deficiency, particularly within the subset of stage I lung adenocarcinoma.

2 months ago

Real-world evidence • Journal • PD(L)-1 Biomarker • IO biomarker • Real-world • Metastases

PD-L1 (Programmed death ligand 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

PD-L1 expression • CDKN2A deletion • CDKN2A expression

PD-L1 IHC 22C3 pharmDx

2ms

Integrated assessment of malignancy in IDH-mutant astrocytoma with p16 and methylthioadenosine phosphorylase immunohistochemistry. (PubMed, Neuropathology)

Importantly, we revealed contributing factors to gray-zone IHC results (p16: 5-20%, MTAP: mosaic), including (1) hemizygous deletion of CDKN2A, (2) degenerative findings, and (3) intratumoral CDKN2A HD heterogeneity, the detailed histologic and molecular assessment of which would be a key to achieving integrated assessment of malignancy in IDH-mutant astrocytoma. We characterized the pitfalls of each method and provided for the first time a practical flowchart of astrocytoma grading, contributing to a normalization of WHO2021-based molecular diagnostics in resource-limited settings.

2 months ago

Journal

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

CDKN2A deletion • CDKN2A mutation

2ms

Characterisation of cells markers associated with IKZF1plus in BCP-ALL. (PubMed, Transl Oncol)

In this scenario, we found associations between IKZF1plus and certain genes in BCP-ALL, being KCNA5 and GREB1 the most promising biomarkers for predicting IKZF1plus. A deeper understanding of these genetic profiles will allow a better risk assessment and offer precise rationale for therapeutic strategies in BCP-ALL.

2 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • IKZF1 (IKAROS Family Zinc Finger 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5) • CD200 (CD200 Molecule) • BTLA (B And T Lymphocyte Associated) • SDK1 (Sidekick Cell Adhesion Molecule 1) • VPREB1 (V-Set Pre-B Cell Surrogate Light Chain 1)

CDKN2A deletion • IKZF1 deletion • VPREB1 deletion

2ms

Study of Ribociclib and Everolimus in HGG and DIPG (clinicaltrials.gov)

P2, N=100, Recruiting, Nationwide Children's Hospital | Not yet recruiting --> Recruiting

2 months ago

Enrollment open

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) • CCND1 (Cyclin D1) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PIK3R1 (Phosphoinositide-3-Kinase Regulatory Subunit 1) • CDK6 (Cyclin-dependent kinase 6) • CCND2 (Cyclin D2) • CDKN2C (Cyclin Dependent Kinase Inhibitor 2C)

PIK3CA mutation • PTEN mutation • CDKN2A deletion • PIK3CA amplification • CCND1 amplification • CDK4 amplification • PIK3R1 mutation

everolimus • Kisqali (ribociclib)

2ms

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.

2 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

2ms

AB095. Methylation class infant-type hemispheric glioma with CDKN2A/B deletion: a rare case report. (PubMed, Chin Clin Oncol)

Methylation class (MC) infant-type hemispheric glioma may present with macrocephaly. On magnetic resonance imaging (MRI) it may appear as large multi-loculated cystic lesion and irregular contrast enhancing border. The key diagnostic criteria for infant-type hemispheric glioma involve combination of clinical, pathological, and molecular feature.

2 months ago

Journal

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

CDKN2A deletion

2ms

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.

2 months ago

P1 data • Journal

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

CDKN2A deletion • MTAP deletion

AMG 193

2ms

Comprehensive genetic analysis by targeted sequencing identifies risk factors and predicts patient outcome in Mantle Cell Lymphoma: results from the EU-MCL network trials. (PubMed, Leukemia)

Genetic complexity (≥3 CNVs) observed in 51% of analysed patients was significantly associated with impaired FFS and OS. We demonstrate that targeted sequencing from peripheral blood and bone marrow reliably detects diagnostically and prognostically important genetic factors in MCL patients, facilitating genetic characterization in clinical routine.

2 months ago

Journal

TP53 (Tumor protein P53) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • RB1 (RB Transcriptional Corepressor 1) • CCND1 (Cyclin D1) • CXCR4 (Chemokine (C-X-C motif) receptor 4) • KMT2D (Lysine Methyltransferase 2D) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • BIRC3 (Baculoviral IAP repeat containing 3) • NFKBIE (NFKB Inhibitor Epsilon)

TP53 mutation • ATM mutation • CDKN2A deletion

2ms

A fibroblastic reticular cell tumour as unexpected diagnosis (ECP 2024)

Fibroblastic reticular cell tumour (FRCT) is a rare tumour with 21 cases reported in the literature. FRCTs are characterized by cells arranged in a whorls, fascicles or sheets accompanied by lymphoplasmacytic infiltrate. FRCT shows overlapping morphological features with follicular dendritic cell sarcoma (FDCS) and interdigitating dendritic cell sarcoma (IDCS).

2 months ago

IO biomarker

ALK (Anaplastic lymphoma kinase) • KIT (KIT proto-oncogene, receptor tyrosine kinase) • BCL2 (B-cell CLL/lymphoma 2) • CD20 (Membrane Spanning 4-Domains A1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TNFRSF8 (TNF Receptor Superfamily Member 8) • BCL6 (B-cell CLL/lymphoma 6) • CD38 (CD38 Molecule) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CD123 (Interleukin 3 Receptor Subunit Alpha) • EWSR1 (EWS RNA Binding Protein 1) • PAX5 (Paired Box 5) • ALPP (Alkaline Phosphatase, Placental) • CD4 (CD4 Molecule) • CXCL13 (Chemokine (C-X-C motif) ligand 13) • VIM (Vimentin) • CD68 (CD68 Molecule) • IRF4 (Interferon regulatory factor 4) • MME (Membrane Metalloendopeptidase) • IL3RA (Interleukin 3 Receptor Subunit Alpha) • SALL4 (Spalt Like Transcription Factor 4) • TP63 (Tumor protein 63) • PAX8 (Paired box 8) • SPN (Sialophorin) • CR1 (Complement C3b/C4b Receptor 1)

CDKN2A deletion • VIM expression

Archer® FusionPlex® Sarcoma kit

6ms

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.

6 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

6ms

Mesothelioma carcinogenesis of chrysotile and forsterite compared and validated by intraperitoneal injection in rat. (PubMed, Ind Health)

Furthermore, there was a significant homozygous deletion of the CDKN2A/p16 gene in the chrysotile group compared to the control group, in contrast to no significant difference in the FO-1000 and EN-1500 groups. Therefore, this study provides clear evidence that forsterite is a nonmesothelioma carcinogen and suggests that forsterite and enstatite are sufficient substances for chrysotile detoxification.

6 months ago

Preclinical • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MSLN (Mesothelin)

CDKN2A deletion

6ms

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.

6 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion

6ms

The Molecular Landscape of Primary CNS Lymphomas (PCNSLs) in Children and Young Adults. (PubMed, Cancers (Basel))

Immunophenotypically, the cases were predominantly GCB, in contrast to older adults (61%). In summary, we showed that molecular findings identified in the PCNSLs of the older patients were only sparingly present in pediatric and young adult patients.

6 months ago

Journal • IO biomarker

BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CCND1 (Cyclin D1) • BCL6 (B-cell CLL/lymphoma 6) • CARD11 (Caspase Recruitment Domain Family Member 11) • IRF4 (Interferon regulatory factor 4)

CDKN2A deletion • MYD88 mutation • MYD88 L265P • CARD11 mutation • BCL2 rearrangement

6ms

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.

6 months ago

Journal

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

CDKN2A deletion • CDK4 mutation

Ibrance (palbociclib) • Verzenio (abemaciclib)

7ms

Ganglioglioma with anaplastic/high-grade transformation: Histopathologic, molecular, and epigenetic characterization of 3 cases. (PubMed, J Neuropathol Exp Neurol)

By DNA methylation profiling, all primary and recurrent tumors either grouped or definitely matched to different methylation classes. Our findings indicate that malignant progression of the glial component can occur in GG and suggest that CDKN2A/B inactivation plays a significant role in this process.

7 months ago

Journal

BRAF (B-raf proto-oncogene) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

BRAF V600E • BRAF V600 • CDKN2A deletion • CDKN2A mutation

7ms

Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma. (PubMed, Neurology)

This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.

7 months ago

Retrospective data • Journal

IDH1 (Isocitrate dehydrogenase (NADP(+)) 1) • IDH2 (Isocitrate Dehydrogenase (NADP(+)) 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion

7ms

Methylthioadenosine phosphorylase and p16 as surrogate diagnostic markers for CDKN2A homozygous deletion in brain tumors (PubMed, Zhonghua Bing Li Xue Za Zhi)

MTAP could serve as a predictive surrogate for CDKN2A homozygous deletion in adult IDH-mutant astrocytoma, PXA, adult IDH-wildtype glioblastoma and meningioma. However, p16 could only be used in the first two tumor types, and its specificity and sensitivity are lower than that of MTAP.

7 months ago

Journal

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

CDKN2A deletion • IDH wild-type

7ms

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.

7 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