Aging and the rise of somatic cancer-associated mutations in normal tissues

PLoS Genet. 2018 Jan 4;14(1):e1007108. doi: 10.1371/journal.pgen.1007108. eCollection 2018 Jan.

Abstract

DNA mutations are inevitable. Despite proficient DNA repair mechanisms, somatic cells accumulate mutations during development and aging, generating cells with different genotypes within the same individual, a phenomenon known as somatic mosaicism. While the existence of somatic mosaicism has long been recognized, in the last five years, advances in sequencing have provided unprecedented resolution to characterize the extent and nature of somatic genetic variation. Collectively, these new studies are revealing a previously uncharacterized aging phenotype: the accumulation of clones with cancer driver mutations. Here, we summarize the most recent findings, which converge in the novel notion that cancer-associated mutations are prevalent in normal tissue and accumulate with aging.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Aging / genetics*
  • Clone Cells
  • DNA Repair / genetics
  • Databases, Genetic
  • Humans
  • Mosaicism
  • Mutation / genetics
  • Neoplasms / genetics*
  • Phenotype