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

• Published in: EBioMedicine Vol. 8; no. C; pp. 30 - 39
• Main Authors: Zhao, Ran, Choi, Bu Young, Lee, Mee-Hyun, Bode, Ann M., Dong, Zigang
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 01.06.2016; Elsevier
• Subjects: Anticarcinogenic Agents - chemistry; Anticarcinogenic Agents - metabolism; Anticarcinogenic Agents - therapeutic use; Cancer; CDKN2A; 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; Epigenetic alterations; Gene Silencing; Genetic alterations; Humans; Neoplasms - drug therapy; Neoplasms - genetics; Neoplasms - metabolism; Neoplasms - pathology; p16INK4a; Review; Epigenetic alterations; CDKN2A; p16INK4a; Genetic alterations; Cancer; p16(INK4a)
• ISSN: 2352-3964; 2352-3964
• DOI: 10.1016/j.ebiom.2016.04.017

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 p16INK4a protein, has a causal link with several different types of cancers. The p16INK4a 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. •The status of CDKN2A provides epigenetic/genetic information for the cancer patient.•The correlation of p16INK4a and related biomarkers should be considered for prognosis of cancers.•Epigenetic/genetic modulation of changes in CDKN2A might be a promising cancer preventive/therapeutic strategy.