Detecting Somatic Mutations in Normal Cells

Trends Genet. 2018 Jul;34(7):545-557. doi: 10.1016/j.tig.2018.04.003. Epub 2018 May 3.


Somatic mutations have been studied extensively in the context of cancer. Recent studies have demonstrated that high-throughput sequencing data can be used to detect somatic mutations in non-tumor cells. Analysis of such mutations allows us to better understand the mutational processes in normal cells, explore cell lineages in development, and examine potential associations with age-related disease. We describe here approaches for characterizing somatic mutations in normal and non-tumor disease tissues. We discuss several experimental designs and common pitfalls in somatic mutation detection, as well as more recent developments such as phasing and linked-read technology. With the dramatically increasing numbers of samples undergoing genome sequencing, bioinformatic analysis will enable the characterization of somatic mutations and their impact on non-cancer tissues.

Keywords: cell lineage; linked reads; mosaicism; phasing; single-nucleotide variants.

Publication types

  • Review

MeSH terms

  • Animals
  • Computational Biology / methods
  • High-Throughput Nucleotide Sequencing / methods
  • Humans
  • Mutation / genetics*
  • Neoplasms / genetics