Cookies on this website
We use cookies to ensure that we give you the best experience on our website. If you click 'Continue' we'll assume that you are happy to receive all cookies and you won't see this message again. Click 'Find out more' for information on how to change your cookie settings.

It is not clear whether APC mutations are sufficient for early colorectal adenomas to grow or whether additional mutations at other loci are required. We previously have screened 210 early colorectal adenomas from familial adenomatous polyposis patients for mutations and allelic loss at APC. Here, we determined whether allelic loss at APC had any effect on the nearby alpha-catenin gene. However, loss on 5q in familial adenomatous polyposis adenomas rarely extended as far as alpha-catenin, and no differences in alpha-catenin protein expression were found in tumors that showed loss encompassing both APC and alpha-catenin. We then screened all 210 tumors for mutations at candidate loci other than APC (K-ras, beta-catenin, and allelic loss at 1p33-p35 and 1p36) and for microsatellite instability (MSI). Each of these loci has been implicated previously in early colorectal tumorigenesis. One tumor harbored a beta-catenin mutation and another MSI, but none showed K-ras mutation or allelic loss at 1p33-p35 or 1p36. These data support the following hypotheses derived from sporadic colorectal tumors: beta-catenin mutations are generally an alternative to mutations at APC, MSI is not usually an early phenomenon in colorectal tumorigenesis, and K-ras mutations are more typical of large- and moderate-sized adenomas. Contrary to some previous reports, chromosome 1p allelic loss is infrequent in very early adenomas. APC mutations are generally sufficient for colorectal tumors to grow to about 1-cm diameter, although chance mutations at other loci can provide these early colorectal adenomas with a selective advantage, and some colorectal tumors may develop along a pathway not involving APC.

Original publication

DOI

10.1073/pnas.040564697

Type

Journal article

Journal

Proc Natl Acad Sci U S A

Publication Date

29/02/2000

Volume

97

Pages

2225 - 2228

Keywords

Adenoma, Adenomatous Polyposis Coli, Adenomatous Polyposis Coli Protein, Cytoskeletal Proteins, Germ-Line Mutation, Humans