|Amino Acid Change||H83Y|
|Transcript ID (GRCh37/hg19)||ENST00000498124|
|Tumor Type||Primary Site|
CDKN2A H83Y lies within the ANK3 domain of the CDKN2A protein. H83Y confers a loss of function to the CDKN2A protein as demonstrated by loss of cell cycle control. 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 mutations account for only 1-3% of glioblastomas and the clinical significance remains to be elucidated.
Somatic mutations of CDKN2A are present in various tumor types, including, squamous cell carcinoma of the lung, clear cell sarcoma, head and neck cancer, melanoma and esophageal cancer. 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. Multiple preclinical and clinical studies are ongoing for CDKN2A deficient tumors in multiple tumor types.