Gene | CDKN2A |
Variant | CNV |
Transcript ID (GRCh37/hg19) | ENST00000498124 |
Germline/Somatic? | Somatic |
Tumor Type | Primary Site |
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The CDKN2A gene locus is altered in up to approximately 57% of glioblastoma, most commonly as a homozygous deletion, and frequently with concurrent deletion of the CDKN2B locus. CDKN2A/CDKN2B loss may be associated with increased sensitivity to CDK4/6 inhibitors. The efficacy and toxicity profiles of these inhibitors in the context of a variety of cancer types are currently under evaluation in clinical trials.
CDKN2A gene encodes p16 and functions as an important tumor suppressor in various human malignancies. Its activation prevents carcinogenesis via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Genetic alterations (deletion, mutation, and methylation) in p16 associated with loss of function have been reported in cell lines and primary thyroid tumors. However, predictive or prognostic significance of p16 in thyroid cancer is not clear and correlation with other clinical and lab findings is necessary. Multiple clinical trials are available for patients with CDKN2A deficient tumors.
CDKN2A generates several transcript variants including p16 and p14ARF. P16 regulates cell cycle by inhibiting CDK4 and CDK6, and thus preventing progression from G1 to S phase. P14ARF acts as a tumor suppressor by inhibiting ribosome biogenesis and initiating p53-dependent cell cycle arrest and apoptosis. Mutations and deletion of CDKN2A are reported in up to 34% of gastric cancer. In addition, EBV-positive gastric adenocarcinoma showed CDKN2A promoter hypermethylation. Gastric cancer with CDKN2A mutations has been shown to be sensitive to CDK4/6 inhibitors in vitro studies. However, predictive or prognostic significance of CDKN2A mutation in gastric cancer is not clear and correlation with other clinical and laboratory findings is necessary. Multiple clinical trials are available for patients with CDKN2A deficient tumors.
CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. CDKN2A is the major high-risk susceptibility gene identified in melanoma. Somatic mutations of CDKN2A are reported in up to 19% and 20% of cutaneous and desmoplastic melanoma, respectively. Germline mutations have been reported in ~20-40% of families with melanoma. Correlation with other clinical and lab findings is necessary.
CDKN2A gene functions as an important tumor suppressor via induction of cell growth arrest and senescence. Majority of the CDKN2A mutations result in loss or decreased binding to CDK4/6 leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Somatic mutations of CDKN2A are present in various tumor types including ~2-3% of hepatocellular carcinoma (HCC). However, epigenetic silencing of CDKN2A by promoter hypermethylation is more frequent, occurring in 73% of HCC, 56% of HBV-related HCC, and 84% of HCV-related HCC. Clinical trials for CDKN2A deficient tumors are available. Correlation with other clinical and lab findings is necessary.
CDKN2A gene encodes p16 and functions as an important tumor suppressor in various human malignancies. Its activation prevents carcinogenesis via induction of cell growth arrest and senescence. The majority of the CDKN2A mutations span exon 2 and result in loss or decreased binding to CDK4/6, leading to uncontrolled cell growth through inactivation of Rb and p53 pathways. Genetic alterations in CDKN2A have been reported in up to 41% of pancreatic adenocarcinomas (36% CNV loss and 5% SNV alterations). Few studies have suggested that CDKN2A is a causative gene in familial pancreatic cancer families. Germline mutations of CDKN2A among patients with pancreatic cancer are rare (<1%), with estimated penetrance of 58% and 39% for pancreatic cancer and melanoma, respectively. Multiple clinical trials are available for patients with CDKN2A deficient tumors. Predictive and prognostic significance of CDKN2A alterations in pancreatic cancer is not clear and correlation with other clinical and lab findings is necessary.
This gene is a known cancer gene.