Journal article

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

Peter Georgeson, Bernard Pope, Christophe Rosty, Mark Clendenning, Romy Walker, Khalid Mahmood, Jihoon Joo, Ryan Hutchinson, Susan Preston, Julia Como, Sharelle Joseland, Aung Ko Win, Finlay Macrae, John Hopper, Mark Jenkins, Ingrid Winship, Daniel Buchanan

Published : 2019


Objective: Germline pathogenic variants (PVs) in the DNA mismatch repair (MMR) genes and the base excision repair genes NTHL1 and MUTYH underlie hereditary CRC and polyposis syndromes. We evaluate the robustness and discriminatory potential of tumour mutational signatures in colorectal cancers (CRCs) for identifying germline PV carriers. Design: Whole exome sequencing of FFPE CRC tissue was performed on hereditary CRC PV carriers (14 MMR, 6 biallelic MUTYH, and 1 biallelic NTHL1), 9 sporadic MMR-deficient CRCs (MMRd controls) and 18 sporadic MMR-proficient CRCs (MMRp controls). COSMIC V3 Single Base Substitution (SBS) and Indel (ID) mutational signatures were calculated and assessed for thei..

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