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Science DOI:10.1126/science.aaw0726

RNA sequence analysis reveals macroscopic somatic clonal expansion across normal tissues.

Publication TypeJournal Article
Year of Publication2019
AuthorsYizhak, K, Aguet, F, Kim, J, Hess, JM, Kübler, K, Grimsby, J, Frazer, R, Zhang, H, Haradhvala, NJ, Rosebrock, D, Livitz, D, Li, X, Arich-Landkof, E, Shoresh, N, Stewart, C, Segrè, AV, Branton, PA, Polak, P, Ardlie, KG, Getz, G
JournalScience
Volume364
Issue6444
Date Published2019 06 07
ISSN1095-9203
Abstract

How somatic mutations accumulate in normal cells is poorly understood. A comprehensive analysis of RNA sequencing data from ~6700 samples across 29 normal tissues revealed multiple somatic variants, demonstrating that macroscopic clones can be found in many normal tissues. We found that sun-exposed skin, esophagus, and lung have a higher mutation burden than other tested tissues, which suggests that environmental factors can promote somatic mosaicism. Mutation burden was associated with both age and tissue-specific cell proliferation rate, highlighting that mutations accumulate over both time and number of cell divisions. Finally, normal tissues were found to harbor mutations in known cancer genes and hotspots. This study provides a broad view of macroscopic clonal expansion in human tissues, thus serving as a foundation for associating clonal expansion with environmental factors, aging, and risk of disease.

DOI10.1126/science.aaw0726
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/31171663?dopt=Abstract

Alternate JournalScience
PubMed ID31171663