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CDKN2A
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Interpretation 2336
Tier 2
CDKN2A
Variants
CDKN2A R128W
Primary Sites
Colon
Tumor Types
Adenocarcinoma
Interpretation

CDKN2A gene functions as an important tumor suppressor in various human malignancies including colorectal cancer, and 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. Somatic mutations of CDKN2A are present in various tumor types but have not been well characterized in colorectal cancer. However, epigenetic silencing of CDKN2A by hypermethylation has been reported to be a possible predictive factor of poor prognosis in patients with colorectal cancer. CDKN2A R128W is predicted to confer a loss of function to the CDKN2A protein, as demonstrated by a loss of Sp1 binding. CDKN2A R128Q has been shown to be associated with dysplasia in the setting of Barrett's esophagus. However, its prognostic and therapeutic significance in colorectal carcinomas remains to be fully elucidated.

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. Xing X, et al. The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis. Br J Cancer 2013;108(12):2542-8
  4. Sebastian S. Zeki, Shabuddin Khan, Trevor A. Graham, Simon Leedham, Hugh Barr, Neil A. Shepherd, Marco Novelli, Manuel Rodriguez-Justo, Nicholas A. Wright, Stuart A.McDonald Barretts Related Adenocarcinomas Arise as a Monoclonal Outgrowth From Polyclonal Dysplasia https://www.gastrojournal.org/article/S0016-5085(12)62478-0/pdf
  5. Al-Khalaf, HH. Et al. The cyclin-dependent kinase inhibitor p16INK4a physically interacts with transcription factor Sp1 and cyclin-dependent kinase 4 to transactivate microRNA-141 and microRNA-146b-5p spontaneously and in response to ultraviolet light-induced DNA damage. J Biol Chem. 2013 Dec 6;288(49):35511-25.
Last updated: 2019-02-22 18:07:06 UTC
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