COMMENTARY

Colorectal cancer

Top down or bottom up? Competing management structures in the morphogenesis of colorectal neoplasms

N A Wright, R Poulsom

Histopathology Unit, Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK, and Department of Histopathology, Bart’s and the London, Queen Mary’s School of Medicine and Dentistry, University of London, London, UK

Correspondence to:
Correspondence to:
Professor N A Wright, Histopathology Unit, Cancer Research UK, 44 Lincoln’s Inn Fields, London WC2A 3PX, UK;
warden@qmul.ac.uk

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Modifier genes may influence the severity, or adenoma number, of familial adenomatous polyposis in humans through tumour initiation rather than progression

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Keywords: familial adenomatous polyposis; APC; modifier genes; genotype-phenotype association; colon; polyps

The first 150 words of the full text of this article appear below.

One of the earliest tumour suppressor genes to be identified was APC. Germline mutations in APC are found in familial adenomatous polyposis (FAP) and second hits lead to the development of often many hundreds of adenomas in the colon and rectum, some of which progress to cancer if untreated. Many sporadic adenomas, and their ensuing carcinomas, show APC mutations, and FAP remains an important paradigm for the commoner sporadic form. Thus recent studies from the Tomlinson laboratory¹ show a very close linear relationship between the macroscopic—or naked eye—count of adenomas in excised FAP colons and the count made microscopically from adenomas occupying one crypt (the unicryptal or monocryptal adenoma, fig 1) upwards. Such a close relationship strongly indicates that progression from microadenomas to macroscopic size is essentially random, that variation in disease severity (number of adenomas) results from differences in the number of microadenomas rather than disease . . . [Full text of this article]

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Relevant Article

Explaining variation in familial adenomatous polyposis: relationship between genotype and phenotype and evidence for modifier genes

M D Crabtree, I P M Tomlinson, S V Hodgson, K Neale, R K S Phillips, and R S Houlston
Gut 2002 51: 420-423. [Abstract] [Full Text] [PDF]

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