Different combinations of biallelic APC mutation confer different growth advantages in colorectal tumours

Cheadle, Jeremy Peter ORCID: https://orcid.org/0000-0001-9453-8458, Krawczak, Michael, Thomas, Meinir W., Hodges, Angela Kaye, Al-Tassan, Nada, Fleming, Nick and Sampson, Julian Roy ORCID: https://orcid.org/0000-0002-2902-2348 2002. Different combinations of biallelic APC mutation confer different growth advantages in colorectal tumours. Cancer Research 62 (2) , pp. 363-366.

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Abstract

New facets to Knudson's [corrected] "two-hit" hypothesis have been proposed recently in relation to adenomatous polyposis coli (APC): protein inactivation may be selected weakly, and the two hits may be interdependent. We reviewed published data on 165 sporadic and 102 familial adenomatous polyposis-associated colorectal tumors with two characterized mutations. Using a Poisson model, we redefined the mutation cluster region (MCR) to residues 1281-1556 and confirmed that the locations of pairs of APC mutations are interdependent (P < 0.0001). A mathematical model, based on the data for sporadic tumors, implied different growth advantages for different combinations of APC mutations: genotype I/I (I: mutation inside MCR) was 3.9 times more likely to be selected than IO or IL (O: mutation outside MCR, L: allelic loss), which were 27.8 times more likely to be selected than OO or OL.

Item Type:	Article
Date Type:	Publication
Status:	Published
Schools:	Schools > Medicine
Subjects:	R Medicine > R Medicine (General)
Uncontrolled Keywords:	Adenomatous Polyposis Coli/genetics, Alleles, Cell Division/genetics, Colorectal Neoplasms/genetics, Colorectal Neoplasms/pathology, Genes, APC, Genotype, Humans, Models, Genetic, Mutation, Poisson Distribution
Publisher:	American Association for Cancer Research
ISSN:	0008-5472
Last Modified:	25 Oct 2022 09:53
URI:	https://orca.cardiff.ac.uk/id/eprint/60391

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