News - CDKN2A mutation + TP53 mutation

4years

Epigenome-wide analysis of methylation changes in the sequence of gallstone disease, dysplasia, and gallbladder cancer. (PubMed, Hepatology)

Our results indicate that GBC carcinogenesis comprises three main methylation stages: early (gallstone disease and low-grade dysplasia), intermediate (high-grade dysplasia), and late (GBC). The identified gradual changes in methylation and CNVs may help to enhance our understanding of the mechanisms underlying this aggressive disease and eventually lead to improved treatment and early diagnosis of GBC.

4 years ago

Journal

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • CCND1 (Cyclin D1)

CDKN2A mutation + TP53 mutation

over4years

Activation of the RAS pathway through uncommon BRAF mutations in mucinous pancreatic cysts without KRAS mutation. (PubMed, Mod Pathol)

Multiple KRAS mutations correlated with multifocal cysts demonstrated by radiology. In IPMNs that lacked KRAS mutations, the concurring BRAF mutations with GNAS mutations supports an alternate mechanism of activation in the Ras pathway.

over 4 years ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • GNAS (GNAS Complex Locus)

TP53 mutation • BRAF V600E • KRAS mutation • BRAF mutation • CDKN2A mutation + TP53 mutation

over4years

Concurrent TP53 and CDKN2A Gene Aberrations in Newly Diagnosed Mantle Cell Lymphoma Correlate with Chemoresistance and Call for Innovative Upfront Therapy. (PubMed, Cancers (Basel))

Concurrent aberration of TP53 and CDKN2A is a new, simple, and relevant index of chemoresistance in MCL. Patients with concurrent aberration of TP53 and CDKN2A should be offered innovative anti-lymphoma therapy and upfront consolidation with allogeneic stem cell transplantation.

over 4 years ago

Journal

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

TP53 mutation • TP53 deletion • CDKN2A deletion • CDKN2A mutation • CDKN2A mutation + TP53 mutation

over4years

A genomic biomarker-based model for cancer risk stratification of non-dysplastic Barrett's esophagus patients after extended follow up; results from Dutch surveillance cohorts. (PubMed, PLoS One)

The positive and negative predictive values were 0.13 (95% CI 0.09 to 0.19) and 0.97 (95% CI 0.93 to 0.99). We propose the implementation of the model to identify non-dysplastic Barrett's patients, who are required to remain in surveillance programs with 3-yearly surveillance intervals from those that can benefit from less frequent or no surveillance.

over 4 years ago

Clinical • Journal

HER-2 (Human epidermal growth factor receptor 2) • TP53 (Tumor protein P53) • MYC (V-myc avian myelocytomatosis viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

CDKN2A mutation + TP53 mutation

over4years

From Genes to -Omics: The Evolving Molecular Landscape of Malignant Peripheral Nerve Sheath Tumor. (PubMed, Genes (Basel))

However, broader genomic studies have also identified recurrent but less prevalent genetic variants in human MPNST that also contribute to the molecular landscape of MPNST and may inform further research. Future studies to further define the molecular landscape of human MPNST should focus on collaborative efforts across multiple institutions in order to maximize information gathered from large numbers of well-annotated MPNST patient samples, both in the NF1 and the sporadic MPNST populations.

over 4 years ago

Review • Journal

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

TP53 mutation • NF1 mutation • CDKN2A mutation + TP53 mutation

over4years

Assessment of clinical outcomes with immune checkpoint inhibitor therapy in melanoma patients with CDKN2A and TP53 pathogenic mutations. (PubMed, PLoS One)

Cell cycle regulators such as TP53 and CDKN2A do not appear to significantly alter clinical outcomes when immune checkpoint inhibitors are used.

over 4 years ago

Clinical • Clinical data • Journal • Checkpoint inhibition • IO biomarker

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

TP53 mutation • BRAF mutation • CDKN2A mutation • CDKN2A mutation + TP53 mutation

over4years

Analysis of targeted somatic mutations in pleomorphic carcinoma of the lung using next-generation sequencing technique. (PubMed, Thorac Cancer)

Significant findings of the study This study demonstrates that mutations in the TP53 gene are frequently found and co-mutations are sometimes found in pleomorphic carcinoma of the lung using genomic profiling analysis. What this study adds Our results will help to analogize the genetic characteristics and potential target of molecular-targeted agents of pleomorphic carcinoma of the lung.

over 4 years ago

Journal

EGFR (Epidermal growth factor receptor) • HER-2 (Human epidermal growth factor receptor 2) • ALK (Anaplastic lymphoma kinase) • TP53 (Tumor protein P53) • PIK3CA (Phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A)

TP53 mutation • EGFR mutation • PIK3CA mutation • CDKN2A mutation • MET mutation • CDKN2A mutation + TP53 mutation

over4years

Pancreatic ductal adenocarcinomas from Mexican patients present a distinct genomic mutational pattern. (PubMed, Mol Biol Rep)

In addition, we discovered several recurrent putative copy number aberrations in SKP2, BRAF, CSSF1R, FOXE1, JAK2 and MET genes and in genes previously reported as putative drivers in PDAC, including KRAS, SF3B1, BRAF, MYC and MET. Although a larger cohort is needed to validate these findings, our results could be pointing toward potential differences in contributing factors for PDAC in Latin-American populations.

over 4 years ago

Clinical • Journal

HER-2 (Human epidermal growth factor receptor 2) • KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • MET (MET proto-oncogene, receptor tyrosine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • JAK2 (Janus kinase 2) • SF3B1 (Splicing Factor 3b Subunit 1) • SMAD4 (SMAD family member 4)

TP53 mutation • KRAS mutation • CDKN2A mutation + TP53 mutation

over4years

Biomarker-driven phase 2 umbrella trial study for patients with recurrent small cell lung cancer failing platinum-based chemotherapy. (PubMed, Cancer)

To the best of the authors' knowledge, the current study is the first biomarker-driven umbrella study conducted in patients with recurrent SCLC. Although the current study demonstrated the limited clinical efficacy of monotherapy, novel biomarker approaches using other cell cycle inhibitor(s) or combinations warrant further investigation.

over 4 years ago

Clinical • P2 data • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RICTOR (RPTOR Independent Companion Of MTOR Complex 2)

MYC amplification • RICTOR amplification • CDKN2A mutation + TP53 mutation

adavosertib (AZD1775) • barasertib-HQPA (AZD2811) • vistusertib (AZD2014) • barasertib (AZD1152)

over4years

Melanoma with in-frame deletion of MAP2K1: a distinct molecular subtype of cutaneous melanoma mutually exclusive from BRAF, NRAS, and NF1 mutations. (PubMed, Mod Pathol)

In-frame deletions in MAP2K1, previously shown in experimental models to be strongly MAPK-activating, characterized a significant subset of triple wild-type melanoma (2.0%), suggesting a primary oncogenic role for these mutations. Comprehensive genomic profiling of melanomas enables detection of this alteration, which may have implications for potential therapeutic options.

over 4 years ago

Journal • Tumor Mutational Burden

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • TMB (Tumor Mutational Burden) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MAP2K1 (Mitogen-activated protein kinase kinase 1) • NF1 (Neurofibromin 1) • CTNNB1 (Catenin (cadherin-associated protein), beta 1)

TP53 mutation • BRAF mutation • NF1 mutation • MAP2K1 mutation • CDKN2A mutation + TP53 mutation

over4years

[VIRTUAL] Distinct molecular subtypes and a high diagnostic urinary biomarker of upper urinary tract urothelial carcinoma (AUA 2020)

UTUC showed distinct genetic subtypes characterized by discrete sets of mutations and distinct clinical phenotypes, providing unique therapeutic targets and appropriate treatment strategy. Sequencing urinary sediments is a useful, non-invasive biomarker for precise diagnosis and proper treatment. Source of Funding: Dainippon-Sumitomo Pharmaceutical, Inc.

over 4 years ago

PD(L)-1 Biomarker • IO biomarker

PD-L1 (Programmed death ligand 1) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • FGFR3 (Fibroblast growth factor receptor 3) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase) • KMT2D (Lysine Methyltransferase 2D)

TP53 mutation • FGFR3 mutation • CDKN2A mutation + TP53 mutation

over4years

[VIRTUAL] Distinct molecular subtypes and a high diagnostic urinary biomarker of upper urinary tract urothelial carcinoma (AACR-II 2020)

None of the post operative (0/34) and control (0/19) samples showed mutations/CNAs, including two with positive cytology (class4), both of which were diagnosed as benign pelvis tumors after surgery.[Conclusion]UTUC are classified into 5 distinct genetic subtypes characterized by unique profiles of gene mutations, expression and clinical outcomes, which help an optimal choice of therapeutics, including novel molecular-targeted drugs and checkpoint-inhibitors. Sequencing urinary sediments is a useful, non-invasive biomarker for precise diagnosis and proper treatment.

over 4 years ago

PD(L)-1 Biomarker • IO biomarker

TP53 mutation • PD-L1 overexpression • FGFR3 mutation • CDKN2A mutation + TP53 mutation

over4years

[VIRTUAL] CHARACTERISTICS AND CLINICAL SIGNIFICANCE OF GENE MUTATIONS IN RELAPSED OR REFRACTORY PRIMARY MEDIASTINAL B-CELL LYMPHOMA (EHA 2020)

Relapsed or refractory primary mediastinal B cell lymphoma have multiple gene mutations simultaneously, and these gene mutations can involve multiple pathways. Gene mutation screening can provide foundation for accurate treatment of primary mediastinal B cell lymphoma.

over 4 years ago

Clinical • PD(L)-1 Biomarker • IO biomarker

TP53 (Tumor protein P53) • BCL2 (B-cell CLL/lymphoma 2) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MYD88 (MYD88 Innate Immune Signal Transduction Adaptor) • CD8 (cluster of differentiation 8) • EZH2 (Enhancer of zeste 2 polycomb repressive complex 2 subunit) • KMT2D (Lysine Methyltransferase 2D) • B2M (Beta-2-microglobulin) • CREBBP (CREB binding protein) • EP300 (E1A binding protein p300) • FOXO1 (Forkhead box O1) • IRF4 (Interferon regulatory factor 4) • STAT6 (Signal transducer and activator of transcription 6)

CDKN2A mutation + TP53 mutation

over4years

Simple mucinous cysts of the pancreas have heterogeneous somatic mutations. (PubMed, Hum Pathol)

Four cases (31%) had no mutations detected. These findings place the majority of simple mucinous cysts of the pancreas in the spectrum of early, low grade mucinous neoplasia, albeit with an different spectrum of genomic alterations than PanIN and intraductal papillary mucinous neoplasm.

over 4 years ago

Journal

KRAS (KRAS proto-oncogene GTPase) • BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RNF43 (Ring Finger Protein 43) • SMAD4 (SMAD family member 4) • KMT2C (Lysine Methyltransferase 2C)

TP53 mutation • KRAS mutation • BRAF mutation • RNF43 mutation • CDKN2A mutation + TP53 mutation

over4years

[VIRTUAL] Distinct molecular subtypes and a high diagnostic urinary biomarker of upper urinary tract urothelial carcinoma (EAU-I 2020)

over 4 years ago

PD(L)-1 Biomarker • IO biomarker

TP53 mutation • FGFR3 mutation • CDKN2A mutation + TP53 mutation

over4years

[VIRTUAL] Clinical utility of comprehensive genomic pathway and integrated network analyses in personalized oncology. (ASCO 2020)

We discovered that the integrated WfG pathway analyses tool is ideal for visualization of the variants with levels of evidence from clinical literature and FDA drug databases that can help inform treatment options and provides a holistic understanding of a specific tumor profile allowing the treating clinician to select personalized targeted therapy. Research Funding: None

over 4 years ago

Clinical • BRCA Biomarker • PARP Biomarker

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • HRAS (Harvey rat sarcoma viral oncogene homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • RAF1 (Raf-1 Proto-Oncogene Serine/Threonine Kinase) • PARP1 (Poly(ADP-Ribose) Polymerase 1) • MAPK1 (Mitogen-activated protein kinase 1)

CDKN2A mutation + TP53 mutation

over4years

[VIRTUAL] POLO: Homologous recombination repair gene mutations (HRRm) in metastatic pancreatic cancer (mPaC) tumors (AACR-I 2020)

In the Phase III POLO trial (NCT02184195) maintenance olaparib conferred a progression-free survival benefit over placebo in pts with a germline (g) BRCAm and mPaC...Prevalence of mutations in non-HRR genes (CDKN2A, SMAD4, KRAS, TP53) in POLO was consistent with that seen in other pancreatic cancer cohorts.In summary, based on the subgroup of pts with analyzed tumor tissue, the genetic profile of the screened POLO population is reflective of that seen in the overall pancreatic cancer population. ~8% of pts had tumors harboring a BRCAm, with mutations in BRCA2 more prevalent than BRCA1; ~7% of pts had tumors harboring a non-BRCA HRRm, most commonly in ATM (~5%).

over 4 years ago

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) • ATM (ATM serine/threonine kinase) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • SMAD4 (SMAD family member 4) • BRCA (Breast cancer early onset)

TP53 mutation • KRAS mutation • BRCA2 mutation • BRCA1 mutation • ATM mutation • CDKN2A mutation + TP53 mutation

Lynparza (olaparib)

over4years

[VIRTUAL] A phase 1b study of palbociclib + nab-paclitaxel in patients (pts) with metastatic adenocarcinoma of the pancreas (PDAC) (AACR-I 2020)

In Avatar PDAC models, P+ nab-paclitaxel (A) was more effective than either agent alone and similar to P+A+gemcitabine. PD observations were consistent with CDK4/6 inhibition. The combination regimen did not meet the prespecified efficacy threshold.Pfizer (NCT02501902)

over 4 years ago

Clinical • P1 data

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

TP53 mutation • CDKN2A mutation + TP53 mutation

Ibrance (palbociclib) • gemcitabine • albumin-bound paclitaxel

over4years

Aggressive morphologic variants of mantle cell lymphoma characterized with high genomic instability showing frequent chromothripsis, CDKN2A/B loss and TP53 mutations: a multi-institutional study. (PubMed, Genes Chromosomes Cancer)

The non-random chromothripsis events observed in B/P-MCL may be an indicator of clinically aggressive MCL. In addition, frequent CDKN2A deletion and high genomic instability may provide potential targets for alternative treatment.

over 4 years ago

Clinical • Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NOTCH1 (Notch 1) • CCND1 (Cyclin D1) • NOTCH2 (Notch 2) • BIRC3 (Baculoviral IAP repeat containing 3)

TP53 mutation • ATM mutation • CDKN2A mutation + TP53 mutation

over4years

Beyond "Triton": Malignant Peripheral Nerve Sheath Tumors With Complete Heterologous Rhabdomyoblastic Differentiation Mimicking Spindle Cell Rhabdomyosarcoma. (PubMed, Am J Surg Pathol)

MPNST may occasionally show complete heterologous rhabdomyoblastic differentiation without histologic evidence of residual conventional MPNST, closely mimicking spindle cell RMS. IHC for H3K27me3 reliably distinguishes MPNST from spindle cell RMS.

over 4 years ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • NF1 (Neurofibromin 1) • SOX10 (SRY-Box 10) • APP (Amyloid Beta Precursor Protein)

TP53 mutation • NF1 mutation • NF1 deletion • CDKN2A mutation + TP53 mutation

over4years

Burkitt lymphoma: bridging the gap between advances in molecular biology and therapy. (PubMed, Leuk Lymphoma)

The lower-intensity, dose-adjusted EPOCH plus rituximab (DA-EPOCH-R) regimen constitutes a major advance allowing for treatment of older and HIV-positive patients but needs augmentation to better address the central nervous system involvement. Furthermore, DA-EPOCH-R provides a platform for the study of targeted or immunotherapeutic approaches while de-escalating cytotoxic agents and their associated adverse effects. In this review we discuss the epidemiology and molecular genetics of BL, first-line treatment considerations, and potential novel treatment strategies.

over 4 years ago

Journal

TP53 (Tumor protein P53) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • APP (Amyloid Beta Precursor Protein)

TP53 mutation • CDKN2A mutation + TP53 mutation

Rituxan (rituximab)

over4years

Metastatic Melanoma Patient-derived Xenografts Respond to MDM2 Inhibition as a Single Agent or in Combination with BRAF/MEK Inhibition. (PubMed, Clin Cancer Res)

KRT-232 is an effective therapy for the treatment of either BRAF or PAN(BRAF, NRAS) TP53 melanomas. In combination with BRAF and/or MEK inhibitors, KRT-232 may an effective treatment strategy for BRAF mutant tumors.

over 4 years ago

Clinical • Journal • Combination therapy

BRAF (B-raf proto-oncogene) • TP53 (Tumor protein P53) • NRAS (Neuroblastoma RAS viral oncogene homolog) • PTEN (Phosphatase and tensin homolog) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • MDM2 (E3 ubiquitin protein ligase)

TP53 mutation • BRAF mutation • NRAS mutation • PTEN mutation • CDKN2A mutation + TP53 mutation

navtemadlin (KRT-232)

5years

FIRST YEAR EXPERIENCE OF HEREDITARY TESTING IN GYNECOLOGICAL CANCER PATIENTS IN A CLINICAL SETTING IN THE BAHAMAS (IGCS 2019)

Genetic testing at point of care in the Bahamas is feasible and acceptable. Results highlight need for universal hereditary screening for women in the Bahamas with ovarian cancer as this can allow for better treatment options.

5 years ago

Clinical • BRCA Biomarker

TP53 (Tumor protein P53) • BRCA1 (Breast cancer 1, early onset) • BRCA2 (Breast cancer 2, early onset) • PTEN (Phosphatase and tensin homolog) • STK11 (Serine/threonine kinase 11) • CDKN2A (Cyclin Dependent Kinase Inhibitor 2A) • POLE (DNA Polymerase Epsilon) • BAP1 (BRCA1 Associated Protein 1) • PALB2 (Partner and localizer of BRCA2) • MLH1 (MutL homolog 1) • MSH6 (MutS homolog 6) • CDK4 (Cyclin-dependent kinase 4) • MSH2 (MutS Homolog 2) • SMAD4 (SMAD family member 4) • PMS2 (PMS1 protein homolog 2) • BRCA (Breast cancer early onset) • CDH1 (Cadherin 1) • CHEK2 (Checkpoint kinase 2) • BRIP1 (BRCA1 Interacting Protein C-terminal Helicase 1) • POLD1 (DNA Polymerase Delta 1) • RAD51C (RAD51 paralog C) • RAD51D (RAD51 paralog D) • EPCAM (Epithelial cell adhesion molecule) • BARD1 (BRCA1 Associated RING Domain 1) • MUTYH (MutY homolog) • MITF (Melanocyte Inducing Transcription Factor)

BRCA2 mutation • BRCA1 mutation • BRCA2 deletion • BRCA1 deletion • BRCA mutation • CDKN2A mutation + TP53 mutation