Journal article

Evaluating the utility of tumour mutational signatures for identifying hereditary colorectal cancer and polyposis syndrome carriers.

Peter Georgeson, Bernard J Pope, Christophe Rosty, Mark Clendenning, Khalid Mahmood, Jihoon E Joo, Romy Walker, Ryan A Hutchinson, Susan Preston, Julia Como, Sharelle Joseland, Aung Ko Win, Finlay A Macrae, John L Hopper, Dmitri Mouradov, Peter Gibbs, Oliver M Sieber, Dylan E O'Sullivan, Darren R Brenner, Steve Gallinger Show all

Gut | Published : 2021


OBJECTIVE: Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and in the base excision repair gene MUTYH underlie hereditary colorectal cancer (CRC) and polyposis syndromes. We evaluated the robustness and discriminatory potential of tumour mutational signatures in CRCs for identifying germline PV carriers. DESIGN: Whole-exome sequencing of formalin-fixed paraffin-embedded (FFPE) CRC tissue was performed on 33 MMR germline PV carriers, 12 biallelic MUTYH germline PV carriers, 25 sporadic MLH1 methylated MMR-deficient CRCs (MMRd controls) and 160 sporadic MMR-proficient CRCs (MMRp controls) and included 498 TCGA CRC tumours. COSMIC V3 single base substitution (SBS) and ..

View full abstract