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CDKN2A
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Interpretation 2134
Tier 2
CDKN2A
Variants
CDKN2A any frameshift
Primary Sites
Gall Bladder
Tumor Types
Adenocarcinoma
Interpretation

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. CDKN2A alterations are common, occurring in 60-70% of gallbladder carcinomas, by mechanisms including point mutations, chromosomal loss, and promoter methylation. These somatic CDKN2A alterations are associated with a poor prognosis. A frameshift insertion at codon 57 in exon 2 will result in early truncation of the p16 protein. Multiple clinical trials are available for patients with CDKN2A deficient tumors.

Citations
  1. Rayess H, et al. Cellular senescence and tumor suppressor gene p16. Int J Cancer 2012;130(8):1715-25
  2. Collado M, et al. Cellular senescence in cancer and aging. Cell 2007;130(2):223-33
  3. Kim WY, Sharpless NE. The regulation of INK4/ARF in cancer and aging. Cell. 2006 Oct 20;127(2):265-75. Review.
  4. Odze RD and Goldblum JR. Odze and Goldblum Surgical Pathology of the GI Tract, Liver, Biliary Tract and Pancreas, 3rd Edition
  5. Kim YT et al. Genetic alterations in gallbladder adenoma, dysplasia and carcinoma. Cancer Lett. 2001 Aug 10;169(1):59-68.
  6. Li M, et al. Whole-exome and targeted gene sequencing of gallbladder carcinoma identifies recurrent mutations in the ErbB pathway. Nat Genet. 2014 Aug;46(8):872-6.
Last updated: 2018-03-06 18:02:04 UTC
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When using PMKB, please cite: Huang et al., JAMIA 2017


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