News - CDKN2A deletion

Expanding the Morphologic and Molecular Spectrum of Spindle Cell Tumors Associated With TERT Fusions. (PubMed, Genes Chromosomes Cancer)

Thus, our findings suggest that in-frame TERT fusions may drive the pathogenesis of a group of mostly low-grade unclassified sarcomas with fibroblastic/myofibroblastic differentiation. In contrast, TERT fusions may also be detected in other common sarcoma types co-occurring with numerous genomic alterations, likely representing a secondary driver event.

2 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • CTNNB1 (Catenin (cadherin-associated protein), beta 1) • CD34 (CD34 molecule)

CDKN2A deletion

Genomic Analysis of Low-Grade Serous Ovarian Cancer: Clinical and Biological Insights. (PubMed, Cureus)

The cooperative GOG 281/LOGS trial showed that trametinib, an MEK inhibitor (MEKi), was significantly more effective than standard-of-care options (including chemotherapy or hormonal therapy) in increasing progression-free survival (median PFS 13.0 months vs. 7.2 months; hazard ratio 0.48, p < 0.001)...Genomic and multi-omic profiling have revealed actionable vulnerabilities and precision oncology approaches. The advent of biomarker-directed trials, molecular subtyping incorporation, and innovative computational strategies is likely to gradually ameliorate therapy selection and, thereby, finally improve long-term outcomes for patients with this complex disease.

4 days ago

Review • Journal • Tumor mutational burden • IO biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • ER (Estrogen receptor) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • CDH1 (Cadherin 1) • MIR7 (MicroRNA 7) • RASSF1 (Ras Association Domain Family Member 1)

TP53 mutation • KRAS mutation • BRAF mutation • NRAS mutation • HER-2 mutation • CDKN2A deletion

Mekinist (trametinib)

CDKN2A homozygous deletions and TSC2 somatic mutations in metastatic pancreatic neuroendocrine tumors. (PubMed, NPJ Precis Oncol)

Biallelic loss of DNA damage repair genes, ATRX and/or DAXX, was associated with a high fraction of the genome altered in PanNETs, with pathogenic alterations affecting those genes also being associated with a homologous recombination deficiency signature. These findings highlight molecular mechanisms driving PanNET progression and underscore the need for further molecular characterization and tumor evolution studies to evaluate targeted therapies for such a challenging disease.

9 days ago

Journal

HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ATRX (ATRX Chromatin Remodeler) • TSC2 (TSC complex subunit 2) • DAXX (Death-domain associated protein)

HRD • CDKN2A deletion

10d

Exploring Demographic, Clinical, Surgical, and Imaging Features in Relation to CDKN2A/B Status in Meningiomas. (PubMed, World Neurosurg)

In this cohort, demographic, clinical, or radiological features did not reliably predict CDKN2A/B deletion. Several deletion-positive meningiomas were classified as grade 1 or 2, underscoring the disconnect between morphology and molecular grading. These findings support universal CDKN2A/B testing for accurate WHO classification and risk assessment.

10 days ago

Journal

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

CDKN2A deletion

18d

Genomic and Demographic Characteristics of Angiosarcoma as Described in the AACR Project GENIE Registry. (PubMed, Cancers (Basel))

In one of the largest genomic analyses of angiosarcoma to date, we identified recurrent alterations, suggesting potential future therapeutic targets.

18 days ago

Journal

TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • FGFR1 (Fibroblast growth factor receptor 1) • NTRK2 (Neurotrophic tyrosine kinase, receptor, type 2) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • NOTCH1 (Notch 1) • KDR (Kinase insert domain receptor) • MTAP (Methylthioadenosine Phosphorylase) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • ATRX (ATRX Chromatin Remodeler) • NOTCH2 (Notch 2) • FAT1 (FAT atypical cadherin 1) • FLT4 (Fms-related tyrosine kinase 4) • CRKL (CRK Like Proto-Oncogene, Adaptor Protein) • POT1 (Protection of telomeres 1) • MSI2 (Musashi RNA Binding Protein 2) • ZFHX4 (Zinc Finger Homeobox 4)

TP53 mutation • PIK3CA mutation • CDKN2A deletion

25d

Clinical Significance of MTAP Deletions and their Overlap with Concurrent Oncogenic Driver Alterations Including EGFR in Non-Small Cell Lung Cancer. (PubMed, J Thorac Oncol)

MTAP dels frequently co-occur with oncogenic driver alterations and can develop at time of osimertinib resistance. A patient with oncogenic driver-positive, MTAP-del NSCLC had a partial response to PRMT5 inhibitor treatment. This work could inform future trials of PRMT5 and MAT2A inhibitors.

25 days ago

Journal

EGFR (Epidermal growth factor receptor) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • MAT2A (Methionine Adenosyltransferase 2A)

EGFR mutation • CDKN2A deletion • MTAP deletion

MSK-IMPACT

Tagrisso (osimertinib) • BMS‐986504

26d

Establishment and characterization of a novel cell line ICH-BCPALL-3 from B cell precursor acute lymphoblastic leukemia with TCF3::HLF. (PubMed, Hum Cell)

The cytotoxicity assay indicated that the cell line is sensitive to Aurora Kinase B inhibitor, but not to BCL2 inhibitor. This cell line is the first TCF3::HLF-positive BCP-ALL model without the t(17;19) translocation, facilitating research into leukemogenesis and the development of novel treatments for patients with poor prognosis associated with TCF3::HLF-positive BCP-ALL.

26 days ago

Preclinical • Journal • IO biomarker

KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • AKT1 (V-akt murine thymoma viral oncogene homolog 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5) • TCF3 (Transcription Factor 3) • NCOR1 (Nuclear Receptor Corepressor 1) • AURKB (Aurora Kinase B) • VPREB1 (V-Set Pre-B Cell Surrogate Light Chain 1) • ARID5B (AT-Rich Interaction Domain 5B)

CDKN2A deletion • RB1 deletion

Molecular insights into prognostic model for meningiomas treated with stereotactic radiosurgery: negative impacts of 1q gain on tumor control and survival. (PubMed, Acta Neuropathol Commun)

Molecular classification utilizing WES-derived CNAs substantially improves prognostic prediction after SRS for meningiomas. Chromosome 1q gain was a critical biomarker indicating elevated risk for tumor progression and mortality, even among WHO grade 1 tumors.

1 month ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • NF2 (Neurofibromin 2)

CDKN2A deletion

Decoding the genetic complexity in a pediatric case of B-ALL through long-read genomic sequencing and RNA sequencing. (PubMed, Cancer Genet)

Notably, the presence of NUP214::ABL1 identified a clinically actionable target, supporting the use of tyrosine kinase inhibitors (TKIs) such as imatinib. This case underscores the critical role of integrated sequencing approaches in identifying cryptic genetic alterations in B-ALL for precise classification of oncogenic drivers and for targeted therapeutic strategies to improve patient outcomes.

1 month ago

Journal

ABL1 (ABL proto-oncogene 1) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • TSC1 (TSC complex subunit 1) • NUP214 (Nucleoporin 214) • TRB (T Cell Receptor Beta Locus)

CDKN2A deletion • ABL1 fusion

imatinib

MRI-based prediction of DNA methylation grade in IDH-mutant astrocytomas using qualitative imaging features and tumor volumetrics. (PubMed, Neuroradiology)

MRI-derived imaging features facilitate noninvasive prediction of DNA methylation subclass in IDH-mutant astrocytomas.

1 month ago

Journal

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

CDKN2A deletion

Comparison of Cytoplasmic and Nuclear MTAP Loss in Pleural Effusion Cytology: Correlation With Homozygous p16/CDKN2A Deletion. (PubMed, Cytopathology)

Our findings demonstrate that while nuclear and cytoplasmic MTAP loss are concordant in presence, staining patterns and antibody clone selection affect correlation with p16/CDKN2A deletion. Given that pleural effusion cytology is often the initial diagnostic step in PM, standardised MTAP testing protocols are needed to ensure reproducibility and minimise false-negative interpretations, rather than implying improved diagnostic accuracy.

1 month ago

Journal • Pleural effusion

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

CDKN2A deletion

Analysis of comprehensive genomic profiling test for Ewing sarcoma in pediatric patients and adults using the nationwide clinical and genomic database in Japan. (PubMed, Jpn J Clin Oncol)

Compared to previous reports, Japanese ES cases showed lower STAG2 and higher TP53 mutation frequencies. CDKN2A and CDKN2B deletions may serve as prognostic biomarkers indicating unfavorable outcomes.

1 month ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • EWSR1 (EWS RNA Binding Protein 1) • STAG2 (Stromal Antigen 2)

TP53 mutation • CDKN2A deletion

FoundationOne® CDx • MSK-IMPACT