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Science. 2019 Jun 7;364(6444). pii: eaaw0726. doi: 10.1126/science.aaw0726.

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

Author information

1
Broad Institute of MIT and Harvard, Cambridge, MA, USA.
2
Center for Cancer Research, Massachusetts General Hospital, Boston, MA, USA.
3
Harvard Medical School, Boston, MA, USA.
4
Ocular Genomics Institute, Department of Ophthalmology, Massachusetts Eye and Ear, Boston, MA, USA.
5
Biorepositories and Biospecimen Research Branch, Cancer Diagnosis Program, National Cancer Institute, Bethesda, MD, USA.
6
Oncological Sciences, Icahn School of Medicine at Mount Sinai Hospital, New York, NY, USA.
7
Broad Institute of MIT and Harvard, Cambridge, MA, USA. gadgetz@broadinstitute.org.
8
Department of Pathology, Massachusetts General Hospital, Boston, MA, USA.

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.

Comment in

PMID:
31171663
DOI:
10.1126/science.aaw0726
[Indexed for MEDLINE]

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