Trends in Genetics
Volume 37, Issue 10, October 2021, Pages 872-881
Journal home page for Trends in Genetics

Opinion
Somatic mutations provide important and unique insights into the biology of complex diseases

https://doi.org/10.1016/j.tig.2021.06.012Get rights and content
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Highlights

  • Every organ is a micromosaic of cellular clones carrying distinct somatic mutations that compete for space within the tissue but do not always increase cancer risk.

  • Somatic evolution has the potential to affect the disease progress of common complex diseases. There is emerging evidence it can initiate disease, maintain disease once started, and possibly alleviate disease in some cases.

  • The strength of selection of mutations in particular genes appears to vary between individuals. This is likely driven by differences in both lifestyle and environmental factors as well as germline backgrounds.

  • Existing methods for studying somatic evolution in solid tissues do not scale sufficiently to allow for a well-powered genome-wide association study of mutation rates such that further developments are required.

Somatic evolution of cells within the body is well known to lead to cancers. However, spread of somatic mutations within a tissue over time may also contribute to the pathogenesis of non-neoplastic diseases. Recent years have seen the publication of many studies aiming to characterize somatic evolution in healthy tissues. A logical next step is to extend such work to diseased conditions. As our understanding of the interplay between somatic mutations and non-neoplastic disease grows, opportunities for the joint study of germline and somatic variants will present themselves. Here, we present our thoughts on the utility of somatic mutations for understanding both the causes and consequences of common complex disease and the challenges that remain for the joint study of the soma and germline.

Keywords

somatic mutations
clonal expansions
complex disease

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