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Using colorectal cancer as a model, we review some of the insights into cancer evolution afforded by cancer sequencing. These include nonlinear and neutral evolution; polyclonality of driver mutations and parallel evolution in adenomas, although these are rare in carcinomas; the ability of mutational processes to shape evolution against the force of selection; the presence of rare driver genes that function in the same signaling pathways as the longstanding canonical drivers; and the existence of selective windows that constrain the functional effects of cancer driver mutations within limits. Many of these nascent evolutionary paradigms are potentially important for treating colorectal cancers as well as understanding their development.

Original publication

DOI

10.1053/j.gastro.2022.11.049

Type

Journal article

Journal

Gastroenterology

Publication Date

04/2023

Volume

164

Pages

841 - 846

Addresses

Cancer Research UK Edinburgh Centre, Institute of Genetics & Cancer, University of Edinburgh, Edinburgh, United Kingdom.

Keywords

Humans, Carcinoma, Colorectal Neoplasms, Cell Transformation, Neoplastic, Mutation, Carcinogenesis