Implications of Genetic and Epigenetic Alterations of CDKN2A (p16INK4a) in Cancer

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Abstract

Aberrant gene silencing is highly associated with altered cell cycle regulation during carcinogenesis. In particular, silencing of the CDKN2A tumor suppressor gene, which encodes the p16 ^INK4a protein, has a causal link with several different types of cancers. The p16 ^INK4a protein plays an executional role in cell cycle and senescence through the regulation of the cyclin-dependent kinase (CDK) 4/6 and cyclin D complexes. Several genetic and epigenetic aberrations of CDKN2A lead to enhanced tumorigenesis and metastasis with recurrence of cancer and poor prognosis. In these cases, the restoration of genetic and epigenetic reactivation of CDKN2A is a practical approach for the prevention and therapy of cancer. This review highlights the genetic status of CDKN2A as a prognostic and predictive biomarker in various cancers.

Highlights

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The status of CDKN2A provides epigenetic/genetic information for the cancer patient.
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The correlation of p16 ^INK4a and related biomarkers should be considered for prognosis of cancers.
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Epigenetic/genetic modulation of changes in CDKN2A might be a promising cancer preventive/therapeutic strategy.

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Author and article information

Contributors

Mee-Hyun Lee

Zigang Dong

Journal

Journal ID (nlm-ta): EBioMedicine

Journal ID (iso-abbrev): EBioMedicine

Title: EBioMedicine

Publisher: Elsevier

ISSN (Electronic): 2352-3964

Publication date PMC-release: 03 May 2016

Publication date Collection: June 2016

Publication date (Electronic): 03 May 2016

Volume: 8

Pages: 30-39

Affiliations

[a ]China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, Henan 450008, China

[b ]Department of Pharmaceutical Science and Engineering, Seowon University, Cheongju 361-742, South Korea

[c ]The Hormel Institute, University of Minnesota, Austin, MN 55912, USA

Author notes

[* ]Correspondence to: M.-H. Lee, China-US (Henan) Hormel Cancer Institute, No.127, Dongming Road, Jinshui District, Zhengzhou, Henan 450008, China.China-US (Henan) Hormel Cancer InstituteNo.127, Dongming RoadJinshui DistrictZhengzhouHenan450008China mhlee@ 123456hci-cn.org

[** ]Correspondence to: Z. Dong. The Hormel Institute, University of Minnesota, 801 16 ^th Ave NE, Austin MN55912, USA.The Hormel InstituteUniversity of Minnesota801 16 ^th Ave NEAustinMN55912USA zgdong@ 123456hi.umn.edu

Article

Publisher ID: S2352-3964(16)30152-9

DOI: 10.1016/j.ebiom.2016.04.017

PMC ID: 4919535

PubMed ID: 27428416

SO-VID: 93b674c8-179f-4843-8e76-8d7b976bfc38

License:

This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).

History

Date received : 10 February 2016

Date revision received : 1 April 2016

Date accepted : 14 April 2016

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