Role of the p16 tumor suppressor gene in cancer

William H. Liggett, David Sidransky

Research output: Contribution to journalArticlepeer-review

518 Scopus citations


Since its discovery as a CDKI (cyclin-dependent kinase inhibitor) in 1993, the tumor suppressor p16 (INK4A/MTS-1/CDKN2A) has gained widespread importance in cancer. The frequent mutations and deletions of p 16 in human cancer cell lines first suggested an important role for p 16 in carcinogenesis. This genetic evidence for a causal role was significantly strengthened the observation that p16 was frequently inactivated in familial melanoma kindreds. Since then, a high frequency of p16 gene alterations were observed in many primary tumors. In human neoplasms, p16 is silenced in at least three ways: homozygous deletion, methylation of the promoter, and point mutation. The first two mechanisms comprise the majority of inactivation events in most primary tumors. Additionally, the loss of p16 may be an early event in cancer progression, because deletion of at least one copy is quite high in same premalignant lesions. p16 is a major target in carcinogenesis, rivaled in frequency only the p53 tumor-suppressor gene. Its mechanism of action as a CDKI has been elegantly elucidated and involves binding to and inactivating the cyclin D-cyclin-dependent kinase 4 (or 6) complex, and thus renders the retinoblastoma protein inactive. This effect blocks the transcription of important cell-cycle regulatory proteins and results in cell-cycle arrest. Although p16 may be involved in cell senescence, the physiologic role of p16 is still unclear. Future work will focus on studies of the upstream events that lead to p 16 expression and its mechanism of regulation, and perhaps lead to better therapeutic strategies that can improve the clinical course of many lethal cancers.

Original languageEnglish (US)
Pages (from-to)1197-1206
Number of pages10
JournalJournal of Clinical Oncology
Issue number3
StatePublished - Mar 1998

ASJC Scopus subject areas

  • Oncology
  • Cancer Research


Dive into the research topics of 'Role of the p16 tumor suppressor gene in cancer'. Together they form a unique fingerprint.

Cite this