Adenoma development in familial adenomatous polyposis andMUTYH-associated polyposis: somatic landscape and driver genes

Rashid, Mamunur, Fischer, Andrej, Wilson, Cathy H., Tiffen, Jessamy, Rust, Alistair G., Stevens, Philip, Idziaszczyk, Shelley, Maynard, Julie, Williams, Geraint T. ORCID: https://orcid.org/0000-0003-3768-9940, Mustonen, Ville, Sampson, Julian R. ORCID: https://orcid.org/0000-0002-2902-2348 and Adams, David J. 2016. Adenoma development in familial adenomatous polyposis andMUTYH-associated polyposis: somatic landscape and driver genes. Journal of Pathology 238 (1) , pp. 98-108. 10.1002/path.4643

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Abstract

Familial adenomatous polyposis (FAP) and MUTYH‐associated polyposis (MAP) are inherited disorders associated with multiple colorectal adenomas that lead to a very high risk of colorectal cancer. The somatic mutations that drive adenoma development in these conditions have not been investigated comprehensively. In this study we performed analysis of paired colorectal adenoma and normal tissue DNA from individuals with FAP or MAP, sequencing 14 adenoma whole exomes (eight MAP, six FAP), 55 adenoma targeted exomes (33 MAP, 22 FAP) and germline DNA from each patient, and a further 63 adenomas by capillary sequencing (41 FAP, 22 MAP). With these data we examined the profile of mutated genes, the mutational signatures and the somatic mutation rates, observing significant diversity in the constellations of mutated driver genes in different adenomas, and loss‐of‐function mutations in WTX (9%; p < 9.99e‐06), a gene implicated in regulation of the WNT pathway and p53 acetylation. These data extend our understanding of the early events in colorectal tumourigenesis in the polyposis syndromes. © 2015 The Authors. The Journal of Pathology published by John Wiley & Sons Ltd on behalf of Pathological Society of Great Britain and Ireland.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Medicine
Subjects:	R Medicine > R Medicine (General)
Additional Information:	This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Publisher:	Wiley
ISSN:	0022-3417
Date of First Compliant Deposit:	31 March 2016
Date of Acceptance:	21 September 2015
Last Modified:	05 May 2023 01:57
URI:	https://orca.cardiff.ac.uk/id/eprint/88410

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