Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer.

doi:10.1038/s41588-024-01777-9

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Article

Homopolymer switches mediate adaptive mutability in mismatch repair-deficient colorectal cancer.

Nature genetics - 1 Jul 2024

Kayhanian Hamzeh, Cross William, van der Horst Suzanne E M, Barmpoutis Panagiotis, Lakatos Eszter, Caravagna Giulio, Zapata Luis, Van Hoeck Arne, Middelkamp Sjors, Litchfield Kevin, Steele Christopher, Waddingham William, Patel Dominic, Milite Salvatore, Jin Chen, Baker Ann-Marie, Alexander Daniel C, Khan Khurum, Hochhauser Daniel, Novelli Marco, Werner Benjamin, van Boxtel Ruben, Hageman Joris H, Buissant des Amorie Julian R, Linares Josep, Ligtenberg Marjolijn J L, Nagtegaal Iris D, Laclé Miangela M, Moons Leon M G, Brosens Lodewijk A A, Pillay Nischalan, Sottoriva Andrea, Graham Trevor A, Rodriguez-Justo Manuel, Shiu Kai-Keen, Snippert Hugo J G, Jansen Marnix

Abstract excerpt

Mismatch repair (MMR)-deficient cancer evolves through the stepwise erosion of coding homopolymers in target genes. Curiously, the MMR genes MutS homolog 6 (MSH6) and MutS homolog 3 (MSH3) also contain coding homopolymers, and these are frequent mutational targets in MMR-deficient cancers. The impact of incremental MMR mutations on MMR-deficient cancer evolution is unknown. Here we show that microsatellite...

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Identifiers

PMID: 38956208
DOI: 10.1038/s41588-024-01777-9
PMCID: PMC11250277

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PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-08.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

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