Implications of Genetic and Epigenetic Alterations of CDKN2A (p16(INK4a)) in Cancer

EBioMedicine. 2016 Jun:8:30-39. doi: 10.1016/j.ebiom.2016.04.017. Epub 2016 May 3.

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.

Keywords: CDKN2A; Cancer; Epigenetic alterations; Genetic alterations; p16(INK4a).

Publication types

  • Review

MeSH terms

  • Anticarcinogenic Agents / chemistry
  • Anticarcinogenic Agents / metabolism
  • Anticarcinogenic Agents / therapeutic use
  • Cyclin D / genetics
  • Cyclin D / metabolism
  • Cyclin-Dependent Kinase Inhibitor p16 / antagonists & inhibitors
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism*
  • Cyclin-Dependent Kinases / genetics
  • Cyclin-Dependent Kinases / metabolism
  • Epigenesis, Genetic*
  • Gene Silencing
  • Humans
  • Neoplasms / drug therapy
  • Neoplasms / genetics
  • Neoplasms / metabolism
  • Neoplasms / pathology

Substances

  • Anticarcinogenic Agents
  • Cyclin D
  • Cyclin-Dependent Kinase Inhibitor p16
  • Cyclin-Dependent Kinases