Genetics of melanoma progression: the rise and fall of cell senescence

Pigment Cell Melanoma Res. 2016 Mar;29(2):122-40. doi: 10.1111/pcmr.12422. Epub 2015 Nov 18.

Abstract

There are many links between cell senescence and the genetics of melanoma, meaning both familial susceptibility and somatic-genetic changes in sporadic melanoma. For example, CDKN2A, the best-known melanoma susceptibility gene, encodes two effectors of cell senescence, while other familial melanoma genes are related to telomeres and their maintenance. This article aimed to analyze our current knowledge of the genetic or epigenetic driver changes necessary to generate a cutaneous metastatic melanoma, the commonest order in which these occur, and the relation of these changes to the biology and pathology of melanoma progression. Emphasis is laid on the role of cell senescence and the escape from senescence leading to cellular immortality, the ability to divide indefinitely.

Keywords: TERT; immortalization; melanoma; metamortal; nevus; p16; senescence.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Cellular Senescence / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / genetics*
  • Cyclin-Dependent Kinase Inhibitor p16 / metabolism
  • Genetic Predisposition to Disease*
  • Humans
  • Melanoma / genetics*
  • Melanoma / metabolism
  • Melanoma / pathology
  • Neoplasm Metastasis
  • Neoplasm Proteins / genetics*
  • Neoplasm Proteins / metabolism
  • Skin Neoplasms / genetics*
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / pathology
  • Telomere / genetics*
  • Telomere / metabolism
  • Telomere Homeostasis / genetics*

Substances

  • Cyclin-Dependent Kinase Inhibitor p16
  • Neoplasm Proteins