Somatic Mutant Clones Colonize the Human Esophagus with Age

Overview

Journal Science

Specialty Science

Date 2018 Oct 20

PMID 30337457

Citations 492

Authors

Inigo Martincorena

Joanna C Fowler

Agnieszka Wabik

Andrew R J Lawson

Federico Abascal

Michael W J Hall

Alex Cagan

Kasumi Murai

Krishnaa Mahbubani

Michael R Stratton

Rebecca C Fitzgerald

Penny A Handford

Peter J Campbell

Kourosh Saeb-Parsy

Philip H Jones

Affiliations

Soon will be listed here.

Abstract

The extent to which cells in normal tissues accumulate mutations throughout life is poorly understood. Some mutant cells expand into clones that can be detected by genome sequencing. We mapped mutant clones in normal esophageal epithelium from nine donors (age range, 20 to 75 years). Somatic mutations accumulated with age and were caused mainly by intrinsic mutational processes. We found strong positive selection of clones carrying mutations in 14 cancer genes, with tens to hundreds of clones per square centimeter. In middle-aged and elderly donors, clones with cancer-associated mutations covered much of the epithelium, with and mutations affecting 12 to 80% and 2 to 37% of cells, respectively. Unexpectedly, the prevalence of mutations in normal esophagus was several times higher than in esophageal cancers. These findings have implications for our understanding of cancer and aging.

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