NDLI: Location in the large bowel influences the APC mutations observed in FAP adenomas

Content Provider	Springer Nature Link
Author	Will, O. C. Leedham, S. J. Elia, G. Phillips, R. K. S. Clark, S. K. Tomlinson, I. P. M.
Copyright Year	2010
Abstract	The right colon differs from the left, in embryological origin, luminal environment, and function. In both sporadic colorectal cancer and Familial Adenomatous Polyposis (FAP), polyp density and cancer susceptibility vary markedly by colonic site. Adenomas in FAP have a different mutational spectrum in small intestine versus colon. This study aimed to investigate whether colonic location also influences the APC mutation spectrum in FAP. 127 1–2 mm mildly dysplastic adenomas from 5 patients with a codon 1309 germline mutation, and 41 from 3 patients with mutations proximal to codon 1265, were analysed to assess the frequency of loss of heterozygosity (LOH). We chose polyps from different locations in the colon. Immunohistochemistry for beta-catenin, caspase-3 and Ki-67 was performed to assess Wnt pathway activation, apoptosis and proliferation. In polyps from patients with a 1309 mutation, the frequency of LOH showed a gradient from rectum (highest) to caecum/ascending colon (lowest), but this was not present in patients with proximal germline APC mutations. Crypt-by-crypt analysis confirmed the LOH findings from whole polyps. Beta-catenin and caspase-3 expression showed no significant variation by colonic region, but Ki-67 expression decreased from ascending colon to rectum in tumours and normal tissue. Colonic site alters the mutational spectrum of APC, and crypt cell proliferation. The higher frequency of LOH in rectal polyps from patients with codon 1309 mutations may help to explain their increased polyp burden at this site compared with patients who have other germline APC mutations.
Starting Page	389
Ending Page	393
Page Count	5
File Format	PDF
ISSN	13899600
Journal	Familial Cancer
Volume Number	9
Issue Number	3
e-ISSN	15737292
Language	English
Publisher	Springer Netherlands
Publisher Date	2010-03-13
Publisher Place	Dordrecht
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	APC Colorectal cancer ‘just right’ Wnt signalling Two-hit hypothesis Polyposis Biomedicine general Epidemiology Human Genetics Cancer Research
Content Type	Text
Resource Type	Article
Subject	Genetics Cancer Research Genetics (clinical) Oncology

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