News - CDKN2A deletion

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.

8 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

16d

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.

16 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

16d

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.

16 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

21d

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.

21 days ago

Journal

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

CDKN2A deletion

22d

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.

22 days 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

24d

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.

24 days ago

Journal

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

CDKN2A deletion

25d

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.

25 days ago

Journal • Pleural effusion

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

CDKN2A deletion

26d

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.

26 days 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

26d

Single nucleus transcriptomics, pharmacokinetics, and pharmacodynamics of CDK4/6 and mTOR inhibition in a phase 0/1 trial of recurrent high-grade glioma. (PubMed, Neuro Oncol)

This trial underscores the value of integrating pharmacokinetics, pharmacodynamics, and single nucleus transcriptomics in Phase 0/1 surgical studies to assess treatment effects, including malignant cell state shifts. ClinicalTrials.gov identifier: NCT03834740.

26 days ago

PK/PD data • Journal

PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

PIK3CA mutation • CDKN2A deletion • IDH wild-type

everolimus • Kisqali (ribociclib)

29d

MTAP Loss Correlates With Favorable Prognosis in HPV-independent, p16-negative Oropharyngeal Squamous Cell Carcinoma. (PubMed, Am J Surg Pathol)

Because MTAP is related to the methionine salvage pathway, various cancer cell lines with MTAP deletion have been reported to exhibit increased sensitivity to the pyrimidine analog 5-fluorouracil (5-FU)...MTAP deficiency is closely associated with homozygous CDKN2A and MTAP deletions in HPV-negative/p16-negative OPSCCs. Furthermore, MTAP loss may be a favorable prognostic factor in HPV-negative OPSCC, and this paradoxical phenomenon might be explained by the enhanced efficacy of chemotherapy with pyrimidine analogs.

29 days ago

Journal

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

CDKN2A deletion • MTAP deletion

5-fluorouracil

29d

BRAF inhibition increases TGFβ2 production and stimulates metastasis in mice with endogenous BRAFV600E-induced hepatocellular carcinoma. (PubMed, Proc Natl Acad Sci U S A)

While the BRAF inhibitor PLX4720 effectively reduced primary tumors and extended survival, it paradoxically increased sarcomatoid metastases...We conclude that BRAFV600E drives diverse primary tumors but only one type of metastasis and that RAF inhibition, while effective against primary tumors, may promote metastasis through TGFβ2-mediated EMT. Although RAF inhibitors remain promising therapies, their unintended role in enhancing metastasis raises concerns that may extend beyond liver cancer to other BRAFV600E-driven malignancies.

29 days ago

Preclinical • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TGFB1 (Transforming Growth Factor Beta 1) • TGFB2 (Transforming Growth Factor Beta 2)

BRAF V600E • BRAF V600 • CDKN2A deletion

PLX4720

29d

Rare Case of Collecting Duct Carcinoma With Complete Response to Nivolumab. (PubMed, Case Rep Oncol Med)

She was first treated with palbociclib and letrozole, but progression occurred after 3 months. This combined modality approach achieved an unprecedented durable response, underscoring that personalized multimodal therapy-linking radiotherapy, immunotherapy and targeted cell-cycle inhibition-can yield long-term control in CDC. For a disease as lethal as CDC, this outcome demonstrates that genomically informed therapy can achieve extraordinary benefit.

29 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • VIM (Vimentin) • KRT19 (Keratin 19) • PAX8 (Paired box 8)

CDKN2A deletion

Opdivo (nivolumab) • Ibrance (palbociclib) • letrozole