News - CDKN2A mutation

Molecular characteristics and multivariate survival analysis of 43 patients with locally advanced or metastatic esophageal squamous cell carcinoma. (PubMed, J Thorac Dis)

NOTCH1, CBLB and TSC2 alterations were found to be potential indicators of poor prognosis in patients with ESCC. TMB was also positively correlated with the OS of ESCC patients, providing valuable insights for their treatment strategies.

3 days ago

Journal • Tumor mutational burden • Metastases

TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • FGF19 (Fibroblast growth factor 19) • TSC2 (TSC complex subunit 2)

TP53 mutation • NOTCH1 mutation • CDKN2A mutation • TSC2 mutation

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

No abstract available

8 days ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion • CDKN2A mutation

17d

A Pancreatic Cancer Screening Study in Hereditary High Risk Individuals (clinicaltrials.gov)

P=N/A, N=200, Recruiting, Nuvance Health | N=100 --> 200

17 days ago

Enrollment change

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2)

BRCA1 mutation • ATM mutation • PALB2 mutation • CDKN2A mutation • MSH2 mutation • PMS2 mutation

21d

OH2 oncolytic virus: A novel approach to glioblastoma intervention through direct targeting of tumor cells and augmentation of anti-tumor immune responses. (PubMed, Cancer Lett)

Significantly, these discoveries have driven the initiation of a phase I/II clinical trial (ClinicalTrials.gov: NCT05235074). This trial is designed to explore the potential of OH2 as a therapeutic option for patients with recurrent central nervous system tumors following surgical intervention.

21 days ago

Journal • Oncolytic virus • IO biomarker • Tumor cell

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • IDO1 (Indoleamine 2,3-dioxygenase 1) • CD4 (CD4 Molecule)

CDKN2A deletion • CDKN2A mutation

BS001

24d

Rim enhancement of pancreatic ductal adenocarcinoma: investigating the relationship with DCE-MRI-based radiomics and next-generation sequencing. (PubMed, Front Oncol)

Rim enhancement of PDAC is associated with KRAS VAF derived from NGS-based genetic information. For predicting the KRAS VAF status in PDAC, a radiomics model based on DCE maps showed promising results.

24 days ago

Journal • Next-generation sequencing

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4)

KRAS mutation • CDKN2A mutation • SMAD4 mutation

28d

Effect of radiotherapy on head and neck cancer tissues in patients receiving radiotherapy: a bioinformatics analysis-based study. (PubMed, Sci Rep)

In conclusion, the bioinformatics analyses delved into the effect of radiotherapy on patients with head and neck carcinoma. This study provides a theoretical framework elucidating the molecular mechanisms underlying radiotherapy's efficacy in treating head and neck cancer and presents scientific recommendations for drug therapy following radiotherapy.

28 days ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TTN (Titin)

TP53 mutation • CDKN2A mutation

PancreasScan: Pancreatic Cancer Screening for At-risk Individuals (clinicaltrials.gov)

P=N/A, N=500, Recruiting, Beth Israel Deaconess Medical Center | Trial completion date: Jul 2026 --> Mar 2028 | Trial primary completion date: Jul 2025 --> Mar 2027

1 month ago

Trial completion date • Trial primary completion date

BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • ATM (ATM serine/threonine kinase) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • MSH2 (MutS Homolog 2) • BRCA (Breast cancer early onset) • EPCAM (Epithelial cell adhesion molecule) • PRSS1 (Serine Protease 1)

BRCA2 mutation • BRCA1 mutation • PALB2 mutation • CDKN2A mutation • MLH1 mutation • PMS2 mutation • BRCA mutation

Genomic landscape of gynecologic cancers with poor prognosis in Japan, an analysis of the national database of comprehensive genomic profiling tests (AACR 2024)

The C-CAT database offers insights into the mutational landscape of various cancers and histological subtypes, especially those with poor prognosis, highlighting the unmet needs for drug development in these gynecologic cancers.

1 month ago

Tumor mutational burden • MSi-H Biomarker

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A)

TP53 mutation • KRAS mutation • TMB-H • MSI-H/dMMR • PIK3CA mutation • ARID1A mutation • STK11 mutation • CDKN2A mutation

FoundationOne® CDx

Quantitative and Qualitative Parameters of DCE-MRI Predict CDKN2A/B Homozygous Deletion in Gliomas. (PubMed, Acad Radiol)

Ktrans can serve as valuable predictive parameters for identifying CDKN2A/B HD status in all types of gliomas and both subtypes of IDH-mutant and IDH-wild gliomas. These findings provide a foundation for precise preoperative non-invasive diagnosis and personalized treatment approaches for glioma patients.

1 month ago

Journal

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

CDKN2A deletion • CDKN2A mutation

2ms

MELVEC: Melanoma Detection in Switzerland With VECTRA (clinicaltrials.gov)

P=N/A, N=455, Completed, University Hospital, Basel, Switzerland | Recruiting --> Completed | N=720 --> 455

2 months ago

Trial completion • Enrollment change

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A mutation

2ms

Intrahepatic Cholangiocarcinoma Histologic Subtypes Correlate with Hidden-Genome Classification (USCAP 2024)

The majority of IHC with high homology to HCC by hidden-genomic classifier are histologically adenocarcinoma. There is strong correlation between genotype and certain histologic features. Features such as small duct, large duct, and intracellular mucin strongly correlate with one class over other.

2 months ago

KRAS (KRAS proto-oncogene GTPase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • SMAD4 (SMAD family member 4) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

KRAS mutation • CDKN2A mutation • CTNNB1 mutation

MSK-IMPACT

2ms

Pancreas Registry and High Risk Registry (clinicaltrials.gov)

P=N/A, N=1116, Recruiting, Icahn School of Medicine at Mount Sinai | Trial completion date: Dec 2023 --> Nov 2033 | Trial primary completion date: Dec 2023 --> Nov 2033

2 months ago

Trial completion date • Trial primary completion date

ATM mutation • STK11 mutation • PALB2 mutation • CDKN2A mutation

3ms

Cytopathological characteristics of SMARCA4-deficient thoracic undifferentiated tumors in serous effusion (PubMed, Zhonghua Bing Li Xue Za Zhi)

This tumor thus warrants careful consideration. Accurate diagnosis can greatly improve early diagnosis and treatment of these tumors.

3 months ago

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

HER-2 (Human epidermal growth factor receptor 2) • PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA2 (Breast cancer 2, early onset) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • SMARCB1 (SWI/SNF Related, Matrix Associated, Actin Dependent Regulator Of Chromatin, Subfamily B, Member 1) • CD34 (CD34 molecule) • SALL4 (Spalt Like Transcription Factor 4) • SYP (Synaptophysin)

TP53 mutation • HER-2 amplification • MET amplification • STK11 mutation • PD-L1 negative • CDKN2A mutation • MET mutation • BRCA2 deletion • SMARCA4 mutation • BRCA1 deletion

PD-L1 IHC 22C3 pharmDx

3ms

Molecular landscape of proliferative verrucous leukoplakia: a systematic review. (PubMed, Br J Oral Maxillofac Surg)

PVL stroma shows significantly lower α-SMA and higher CD34 expression than OVC and OSCC. The exact genomic landscape is currently unclear, and further studies are necessary to unravel this mystery.

3 months ago

Review • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD34 (CD34 molecule) • ELAVL1 (ELAV Like RNA Binding Protein 1) • CTTN (Cortactin) • SUZ12 (SUZ12 Polycomb Repressive Complex 2 Subunit)

TP53 mutation • CDKN2A mutation • TP53 expression • ELAVL1 expression

3ms

Molecular prognostication in grade 3 meningiomas and p16/MTAP immunohistochemistry for predicting CDKN2A/B status. (PubMed, Neurooncol Adv)

Molecular alterations of grade 3 meningiomas stratify clinical outcomes more so than histologic features alone. Immunohistochemical loss of p16 and MTAP show promise in predicting CDKN2A/B status.

3 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • TERT (Telomerase Reverse Transcriptase) • MTAP (Methylthioadenosine Phosphorylase) • BAP1 (BRCA1 Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

CDKN2A deletion • CDKN2A mutation • BAP1 mutation • TERT mutation

3ms

Eosinophilic Solid and Cystic Renal Cell Carcinoma: Morphologic and Immunohistochemical Study of 18 Cases and Review of the Literature. (PubMed, Arch Pathol Lab Med)

Group 1 (7 of 18; 38.5%) was characterized by positive phospho-4EBP1 and phospho-S6, which can imply hyperactive mechanistic target of rapamycin complex 1 (mTORC1) signaling...One case had metastatic spread and exhibited an aggressive clinical course, and we detected cyclin-dependent kinase inhibitor 2A (CDKN2A) mutation in this case; other patients were alive and without disease progression. Our research proposes that eosinophilic solid and cystic renal cell carcinoma exhibits prototypical pathologic features with CK20 positivity and has aggressive potential.

3 months ago

Review • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF2 (Neurofibromin 2) • EIF4EBP1 (Eukaryotic translation initiation factor 4E binding protein 1)

CDKN2A mutation • NF2 mutation • NF2 negative

sirolimus

3ms

GlioPredictor: a deep learning model for identification of high-risk adult IDH-mutant glioma towards adjuvant treatment planning. (PubMed, Sci Rep)

The current version of GlioPredictor mainly incorporated clinically often tested genetic biomarkers. Considering complexity of clinical and genetic features that correlate with glioma progression, future derivatives of GlioPredictor incorporating more inputs can be a potential supplement for adjuvant radiotherapy patient selection of IDH-mutant glioma patients.

3 months ago

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) • ATRX (ATRX Chromatin Remodeler)

TP53 mutation • EGFR mutation • IDH1 mutation • PTEN mutation • CDKN2A mutation • IDH wild-type

3ms

CDKN2A/B deletion in IDH-mutant astrocytomas: An evaluation by Fluorescence in-situ hybridization. (PubMed, J Neurooncol)

CDKN2A/B-deletion was observed across all the histological grades of IDH-mutant astrocytic tumours, expectedly more in the higher grade. FISH, as a method, can be used for the detection of CDKN2A/B homozygous deletion, when there is concordant interpretation.

3 months ago

Journal

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

CDKN2A deletion • CDKN2A mutation

3ms

Surveillance for Malignant Transformation of Neurofibromatosis Type 1 (NF1) Related Peripheral Nerve Sheath Tumors (PNST) (clinicaltrials.gov)

P=N/A, N=225, Not yet recruiting, National Cancer Institute (NCI)

3 months ago

New trial

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

CDKN2A mutation

3ms

Clinicopathological and Molecular Characteristics of IDH-Wildtype Glioblastoma with FGFR3::TACC3 Fusion. (PubMed, Biomedicines)

Our observations suggest that F3T3-positive GBM is a distinct molecular subgroup of the IDH-wildtype GBM. Both clinicians and pathologists should consider this rare entity in the differential diagnosis of diffuse astrocytic glioma to make an accurate diagnosis and to ensure appropriate therapeutic management.

3 months ago

Journal

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • TERT (Telomerase Reverse Transcriptase) • TACC3 (Transforming acidic coiled-coil containing protein 3) • MDM2 (E3 ubiquitin protein ligase) • CDK4 (Cyclin-dependent kinase 4) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • EGFR mutation • EGFR amplification • PTEN mutation • MDM2 amplification • CDKN2A deletion • CDKN2A mutation • CDK4 amplification • FGFR3 fusion • TERT mutation • IDH wild-type • TERT promoter mutation • CDK4 mutation

3ms

PalboSarc: Trial of Palbociclib in Second Line of Advanced Sarcomas With CDK4 Overexpression. (clinicaltrials.gov)

P2, N=40, Recruiting, Grupo Espanol de Investigacion en Sarcomas | Trial completion date: Dec 2023 --> Sep 2024 | Trial primary completion date: Dec 2023 --> Sep 2024

3 months ago

Trial completion date • Trial primary completion date • Metastases

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4)

CDKN2A mutation • CDK4 overexpression

Ibrance (palbociclib)

3ms

Molecular and Functional Key Features and Oncogenic Drivers in Thymic Carcinomas. (PubMed, Cancers (Basel))

Anti-angiogenic drugs and immune checkpoint inhibitors targeting the PD-1/PD-L1 axis have shown promising results for the treatment of unresectable tumors. Since thymic carcinomas are frankly aggressive tumors, this report presents insights into their oncogenic drivers, categorized under the established hallmarks of cancer.

3 months ago

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

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • CDKN2A mutation

3ms

Enhancing oral squamous cell carcinoma prediction: the prognostic power of the worst pattern of invasion and the limited impact of molecular resection margins. (PubMed, Front Oncol)

Some resection margins that appeared histologically normal harbored tumorigenic mutations in TP53 and CDKN2A genes. Even histologically normal margins may contain molecular alterations that are not detectable by conventional histopathological methods, but NCCN classification system still outperforms other methods in the prediction of the probability of disease relapse.

3 months ago

Journal • BRCA Biomarker

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BRCA (Breast cancer early onset)

TP53 mutation • CDKN2A mutation • BRCA mutation

3ms

Identification of non-actionable mutations with prognostic and predictive value in patients with advanced or metastatic non-small cell lung cancer. (PubMed, Clin Transl Oncol)

Our results provide evidence on the prognostic value of STK11, KEAP1, and CDKN2A/B mutations in patients with aNSCLC. Further research is required to better understand the implications of these findings on patient management and future trial design and treatment selection.

3 months ago

Journal • IO biomarker • Metastases

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • KEAP1 (Kelch Like ECH Associated Protein 1) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B)

TP53 mutation • KRAS mutation • STK11 mutation • KEAP1 mutation • CDKN2A mutation

4ms

Genetic and prognostic analysis of blastoid and pleomorphic mantle cell lymphoma: a multicenter analysis in China. (PubMed, Ann Hematol)

First-line high-dose cytosine arabinoside exposure obtained survival benefits in these populations, and BTKi combination therapy as the front-line treatment had somewhat improvement in survival with no significant difference in the statistic...Patients with POD12 displayed a distinct mutation profile and a poor prognosis. New therapeutic drugs and clinical trials for B/P-MCL need to be further explored.

4 months ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • KMT2D (Lysine Methyltransferase 2D) • SMARCA4 (SWI/SNF related, matrix associated, actin dependent regulator of chromatin, subfamily A, member 4) • NOTCH2 (Notch 2) • CREBBP (CREB binding protein) • FAT1 (FAT atypical cadherin 1) • NSD2 (Nuclear Receptor Binding SET Domain Protein 2)

TP53 mutation • ATM mutation • CDKN2A mutation • KMT2D mutation

cytarabine

4ms

CD8-Lymphocytic Phenotype Significance in Primary Multiple and Familial Melanoma with Various CDKN2A Mutational Status. (PubMed, Medicina (Kaunas))

A higher percentage of CD8-positive intratumoral lymphocytes versus stromal lymphocytes was positively associated with more numerous metastatic sites. The CD8 lymphocytic phenotype harbors major significance in the context of familial and multiple primary melanoma and may comprise a cost-effective investigation meant to help in the establishment of melanoma prognosis and response to immunotherapy.

4 months ago

Journal • IO biomarker

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CD8 (cluster of differentiation 8)

CDKN2A mutation • CD8 positive

4ms

Application of novel PACS-based informatics platform to identify imaging based predictors of CDKN2A allelic status in glioblastomas. (PubMed, Sci Rep)

We developed a novel integrated PACS informatics platform for the assessment of GBM molecular subtypes and show that tumors with HOMDEL are more likely to have radiographic evidence of pial invasion and less likely to have deep white matter invasion or subependymal invasion. These imaging features may allow noninvasive identification of CDKN2A allele status.

4 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A mutation

4ms

Immunophenotypic p14 and p16 correlations with CDKN2A mutations in primary multiple and familial melanoma: An observational study. (PubMed, Medicine (Baltimore))

This analysis highlighted the value of singular p16 immunohistochemical absence as a predictor for aggressive biological behavior and unfavorable prognosis in familial melanoma and/or MPM, in comparison with the exclusive loss of p14, indifferent to the histopathological subtype. The present study emphasizes the utility of immunohistochemistry as a less expensive method of complementing the current testing arsenal and could represent the starting point for the elaboration of tailored diagnostic and therapeutic algorithms, based on the discovered p14-p16-CDKN2A significant correlation.

4 months ago

Observational data • Retrospective data • Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A deletion • CDKN2A mutation • CDKN2A negative

4ms

Exploring the regulatory interactions between mutated genes and homeobox genes in the head and neck cancer progression. (PubMed, Arch Oral Biol)

The interplay between cancer driver genes and HOX genes is pivotal in regulating the oncogenic processes underlying the pathogenesis of head and neck squamous cell carcinoma.

4 months ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • FAT1 (FAT atypical cadherin 1)

TP53 mutation • CDKN2A mutation • FAT1 mutation

4ms

CDKN2A Gene Mutations: Implications for Hereditary Cancer Syndromes. (PubMed, Biomedicines)

Preclinical studies suggest a potential benefit of CDK4/6 inhibitors, although clinical trials show mixed results. This study underscores the importance of continued research into improved diagnostic and therapeutic strategies to address the complexities of hereditary cancer syndromes.

4 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A mutation

4ms

Generation of a Zebrafish Knock-In Model Recapitulating Childhood ETV6::RUNX1-Positive B-Cell Precursor Acute Lymphoblastic Leukemia. (PubMed, Cancers (Basel))

Transcriptomics revealed that the E::R;pax5mut leukemias exclusively represented B-lineage disease. This novel E::R zebrafish model faithfully recapitulates human disease and offers a valuable tool for a more detailed analysis of disease biology in this subtype.

4 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RUNX1 (RUNX Family Transcription Factor 1) • ETV6 (ETS Variant Transcription Factor 6) • CDKN2B (Cyclin Dependent Kinase Inhibitor 2B) • PAX5 (Paired Box 5)

CDKN2A mutation

4ms

Spatial gene expression profiling unveils immuno-oncogenic programs of NF1-associated peripheral nerve sheath tumor progression. (PubMed, Clin Cancer Res)

If validated prospectively in future studies, these signatures may serve as molecular diagnostic tools to augment conventional histopathological diagnosis by identifying neurofibromas at high risk of undergoing malignant transformation, facilitating risk-adapted care.

4 months ago

Journal • IO biomarker

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • BIRC5 (Baculoviral IAP repeat containing 5)

CDKN2A mutation

4ms

Comprehensive review of pancreatic acinar cell carcinoma: epidemiology, diagnosis, molecular features and treatment. (PubMed, Jpn J Clin Oncol)

The response to FOLFIRINOX is generally favourable, and some patients achieve a complete response...Targeted therapies for genomic alternations are beneficial. Therefore, genetic testing is important for patients with pancreatic acinar cell carcinoma to choose the optimal therapeutic strategy.

4 months ago

Review • Journal • BRCA Biomarker • PARP Biomarker

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

TP53 mutation • CDKN2A mutation

5-fluorouracil • irinotecan • leucovorin calcium

4ms

MoleGazer Development Feasibility Study (clinicaltrials.gov)

P=N/A, N=550, Recruiting, Oxford University Hospitals NHS Trust | Trial completion date: Aug 2025 --> Feb 2026 | Trial primary completion date: Aug 2023 --> Feb 2024

4 months ago

Trial completion date • Trial primary completion date

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CDK4 (Cyclin-dependent kinase 4)

CDKN2A mutation • CDK4 mutation

4ms

Germline mutations in pediatric cancer cohort with mixed-ancestry Mexicans. (PubMed, Mol Genet Genomic Med)

This report identifies potential genetic risk factors and provides a better understanding of the underlying mechanisms of childhood cancer in this population.

4 months ago

Journal

CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • MSH6 (MutS homolog 6) • CHEK2 (Checkpoint kinase 2) • FANCA (FA Complementation Group A) • MUTYH (MutY homolog) • DICER1 (Dicer 1 Ribonuclease III)

CDKN2A mutation • CHEK2 mutation • FANCA mutation

4ms

Comprehensive genomic profiling (CGP) of squamous cell carcinoma of unknown primary (SCCUP) presenting with inguinal, pelvic, and retroperitoneal (I/P/RP) metastases. (ASCO-GU 2024)

Fifty-three of 97 (54.6%) patients with SCCUPs presenting with I/P/RP involvement had at least one GA that could potentially guide targeted treatment decisions including entry into biomarker-driven clinical trials. I/P/RP SCCUP patients frequently demonstrated HPV infection and APOBEC mutation signatures. To our knowledge, this is the first report that describes the genomic landscape of SCCUPs presenting with I/P/RP metastases.

4 months ago

Tumor mutational burden • PD(L)-1 Biomarker • MSi-H Biomarker • BRCA Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • TMB (Tumor Mutational Burden) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MSI (Microsatellite instability) • PTEN (Phosphatase and tensin homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MTAP (Methylthioadenosine Phosphorylase) • KMT2D (Lysine Methyltransferase 2D) • ERG (ETS Transcription Factor ERG) • TMPRSS2 (Transmembrane serine protease 2)

PD-L1 expression • TP53 mutation • MSI-H/dMMR • CDKN2A mutation • TMPRSS2-ERG fusion

FoundationOne® CDx

4ms

"De novo replication repair deficient glioblastoma, IDH-wildtype" is a distinct glioblastoma subtype in adults that may benefit from immune checkpoint blockade. (PubMed, Acta Neuropathol)

The median overall survival was 36.8 months, compared to 15.5 months for the other 450 patients (p < 0.001). We conclude that "De novo replication repair deficient glioblastoma, IDH-wildtype" represents a biologically distinct subtype in the adult population that may benefit from prospective identification and treatment with immune checkpoint blockade.

4 months ago

Journal • Checkpoint inhibition • Checkpoint block

EGFR (Epidermal growth factor receptor) • TP53 (Tumor protein P53) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • PDGFRA (Platelet Derived Growth Factor Receptor Alpha) • NF1 (Neurofibromin 1) • TERT (Telomerase Reverse Transcriptase) • ATRX (ATRX Chromatin Remodeler) • SETD2 (SET Domain Containing 2, Histone Lysine Methyltransferase)

TP53 mutation • EGFR amplification • PTEN mutation • NF1 mutation • CDKN2A deletion • CDKN2A mutation • PDGFRA mutation • TERT mutation • IDH wild-type • TERT promoter mutation

4ms

BISCAY: Open-Label, Randomised, Multi-Drug, Biomarker-Directed, Phase 1b Study in Pts w/ Muscle Invasive Bladder Cancer (clinicaltrials.gov)

P1, N=156, Active, not recruiting, AstraZeneca | Phase classification: P1b --> P1 | Trial completion date: Sep 2023 --> Jun 2024

4 months ago

Phase classification • Trial completion date

HRD (Homologous Recombination Deficiency) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RB1 (RB Transcriptional Corepressor 1) • FGFR (Fibroblast Growth Factor Receptor) • CD8 (cluster of differentiation 8) • CCNE1 (Cyclin E1) • MYCN (MYCN Proto-Oncogene BHLH Transcription Factor) • IFNG (Interferon, gamma) • IL6 (Interleukin 6) • IL2 (Interleukin 2) • IL10 (Interleukin 10) • MYCL (MYCL Proto-Oncogene BHLH Transcription Factor)

PD-L1 expression • FGFR3 mutation • CDKN2A deletion • CCNE1 amplification • CDKN2A mutation • FGFR fusion • RB1 deletion • MYCL amplification

Lynparza (olaparib) • Imfinzi (durvalumab) • Koselugo (selumetinib) • adavosertib (AZD1775) • fexagratinib (ABSK091) • vistusertib (AZD2014) • danvatirsen (AZD9150)

4ms

Frequency and oncologic outcomes of KRAS mutations in circulating tumor DNA of patients with pancreatic ductal adenocarcinoma. (ASCO-GI 2024)

Detection of KRAS mutation in liquid biopsies of patients with metastatic PDAC is associated with worse OS. KRAS G12D/Q61 alterations detection is associated with worse OS compared to other KRAS mutation subtypes. Ct-DNA detection of co-occurring CDKN2A mutation is associated with worse OS in patients with KRAS positive metastatic disease.

4 months ago

Clinical • Circulating tumor DNA

KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • ARID1A (AT-rich interaction domain 1A) • SMAD4 (SMAD family member 4)

TP53 mutation • KRAS mutation • KRAS G12D • KRAS G12V • CDKN2A mutation • KRAS G12 • KRAS Q61H • KRAS Q61

4ms

Abemaciclib in patients (pts) with esophageal cancer (EC) with CDKN2A loss or mutation (mut): Results from the Targeted Agent and Profiling Utilization Registry (TAPUR) study. (ASCO-GI 2024)

Abemaciclib monotherapy did not demonstrate sufficient clinical activity in pts with advanced EC with CDKN2A loss or mut for continued evaluation in this pt population. Other tx should be considered for these pts, including tx offered in clinical trials. Clinical trial information: NCT02693535.

4 months ago

Clinical

HER-2 (Human epidermal growth factor receptor 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

HER-2 positive • HER-2 negative • CDKN2A mutation

Verzenio (abemaciclib)

4ms

Evaluation of a real-world clinico-genomics database of patients with upper gastrointestinal (GI) malignancies in Japan. (ASCO-GI 2024)

As part of a nationwide cancer genome screening project, J-SCRUM GI SCREEN database provides comprehensive genomic information for Asian population (Japan). The prevalence of key actionable gene alterations in each tumor type was highly comparable between J-SCRUM GI-SCREEN and TCGA data.

4 months ago

Clinical • Real-world evidence • BRCA Biomarker • Genomic data • Real-world

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • MET (MET proto-oncogene, receptor tyrosine kinase) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NFE2L2 (Nuclear Factor, Erythroid 2 Like 2)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • HER-2 amplification • PIK3CA mutation • MET amplification • KRAS G12D • ATM mutation • KRAS G12V • MYC amplification • CDKN2A mutation • ATM deletion • KRAS G12 • NFE2L2 mutation • KRAS deletion

5ms

A Genomic Approach for High-Grade B Cell Lymphoma with MYC and BCL2 and / or BCL6 Rearrangements: Two Clusters Stood out on Next Generation Sequencing Results (ASH 2023)

Regarding their survival, patients with TP53 pathway alterations should probably not be treated with the standard RCHOP chemo-immunotherapy. Instead, a more intensive immunochemotherapy regimen or novel strategies such as first-line bispecific antibodies or CARTCells might be considered.

5 months ago

Next-generation sequencing • IO biomarker

MYC (V-myc avian myelocytomatosis viral oncogene homolog) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • BCL6 (B-cell CLL/lymphoma 6)

TP53 mutation • LDH elevation • CDKN2A mutation • MYC rearrangement • BCL6 rearrangement • BCL2 rearrangement

Rituxan (rituximab)