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The evolutionary landscape of colorectal tumorigenesis

Research output: Contribution to journalArticle

The S:CORT Consortium

Original languageEnglish
Pages (from-to)1661-1672
Number of pages12
JournalNature Ecology and Evolution
Volume2
Issue number10
DOIs
Accepted/In press12 Jul 2018
Published31 Aug 2018

King's Authors

Abstract

The evolutionary events that cause colorectal adenomas (benign) to progress to carcinomas (malignant) remain largely undetermined. Using multi-region genome and exome sequencing of 24 benign and malignant colorectal tumours, we investigate the evolutionary fitness landscape occupied by these neoplasms. Unlike carcinomas, advanced adenomas frequently harbour sub-clonal driver mutations—considered to be functionally important in the carcinogenic process—that have not swept to fixation, and have relatively high genetic heterogeneity. Carcinomas are distinguished from adenomas by widespread aneusomies that are usually clonal and often accrue in a ‘punctuated’ fashion. We conclude that adenomas evolve across an undulating fitness landscape, whereas carcinomas occupy a sharper fitness peak, probably owing to stabilizing selection.

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