The meaning of p16ink4a expression in tumors: Functional significance, clinical associations and future developments

Agnieszka K. Witkiewicz, Karen E. Knudsen, Adam P. Dicker, Erik S. Knudsen

Research output: Contribution to journalReview articlepeer-review

171 Scopus citations


The CDKN2A gene is a tumor suppressor that encodes the CDK4/6 inhibitor p16ink4a. Loss of this tumor suppressor contributes to the bypass of critical senescent signals and is associated with progression to malignant disease. However, the high-level expression of p16ink4a in tumors is associated with aggressive subtypes of disease, and in certain clinical settings elevated p16ink4a expression is an important determinant for disease prognosis and therapeutic response. These seemingly contradictory facets of p16ink4a expression have lead to confusion related to the meaning of this tumor suppression in tumor pathobiology. As reviewed here, the alternative expression of p16ink4a represents an ideal marker for considering RB-pathway function, tumor heterogeneity and novel means for directing therapy.

Original languageEnglish (US)
Pages (from-to)2497-2503
Number of pages7
JournalCell Cycle
Issue number15
StatePublished - Aug 1 2011


  • CDK
  • CDKN2a
  • Cyclin
  • E2F
  • RB
  • Radiation
  • Therapy
  • p16

ASJC Scopus subject areas

  • Molecular Biology
  • Developmental Biology
  • Cell Biology


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