Cancer-Associated Mutations but No Cancer: Insights into the Early Steps of Carcinogenesis and Implications for Early Cancer Detection

Trends Cancer. 2019 Sep;5(9):531-540. doi: 10.1016/j.trecan.2019.07.007. Epub 2019 Aug 22.

Abstract

Cancer is a disease of aging fueled by the accumulation of somatic mutations. While mutations in tumors are well characterized, little is known about the early mutational processes that initiate tumorigenesis. Recent advances in next-generation sequencing (NGS) have enabled the detection of mutations in normal tissue, revealing an unanticipated high level of age-related somatic mutations affecting most individuals and tissues. Surprisingly, many of these mutations are similar to mutations commonly found in tumors, suggesting an ongoing process of positive selection and clonal expansion akin to what occurs in cancer, but within normal tissue. Here we discuss some of the most important biological and clinical implications of these novel findings, with a special focus on their impact for cancer detection and prediction.

Keywords: aging; cancer-associated mutations; early cancer detection; somatic mutations; tumor evolution.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Aging / genetics*
  • Biomarkers, Tumor / genetics*
  • Carcinogenesis / genetics*
  • DNA Mutational Analysis
  • Early Detection of Cancer / methods*
  • High-Throughput Nucleotide Sequencing
  • Humans
  • Mutation
  • Neoplasms / diagnosis*
  • Neoplasms / genetics
  • Proto-Oncogenes / genetics
  • Tumor Suppressor Proteins / genetics

Substances

  • Biomarkers, Tumor
  • Tumor Suppressor Proteins