Abstract |
Although microsatellite instability (MSI) has been shown to be present in 15% of sporadic colorectal carcinomas, the genetic events underlying the development of these tumors have not been well described. By investigating intratumoral heterogeneity, this study attempts to elucidate whether MSI-positive colorectal carcinomas develop as the result of a random accumulation of mutations or as an ordered, stepwise sequence of genetic alterations. Eighty-six regions from 16 MSI-positive sporadic colorectal carcinomas were examined for mutations in repeat nucleotide sequences of the tumour suppressor genes transforming growth factor beta type II receptor (TGFBRII), insulin-like growth factor II receptor (IGFIIR), and BAX, and the mismatch repair genes MSH3 and MSH6. At least 2 and up to 5 of these genes were mutated in each tumour, and widespread intratumoral heterogeneity was observed for each gene. Regions of tumour with TGFBRII mutations were correlated with a poorly differentiated histology. Unlike the situation in microsatellite stable colorectal carcinomas, the findings of the present study did not suggest that a particular sequence of tumour suppressor and mismatch repair genes are mutated during colorectal tumorigenesis. It seems likely that a random accumulation of mutations, as a result of a defect in the mismatch repair pathway, drives tumour progression in this type of colorectal carcinoma.
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Authors | R Barnetson, J Jass, R Tse, R Eckstein, B Robinson, M Schnitzler |
Journal | Genes, chromosomes & cancer
(Genes Chromosomes Cancer)
Vol. 29
Issue 2
Pg. 130-6
(Oct 2000)
ISSN: 1045-2257 [Print] United States |
PMID | 10959092
(Publication Type: Journal Article)
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Copyright | Copyright 2000 Wiley-Liss, Inc. |
Topics |
- Colorectal Neoplasms
(genetics)
- DNA Mutational Analysis
(methods)
- Genetic Heterogeneity
- Humans
- Microsatellite Repeats
(genetics)
- Mutation
(genetics)
- Trinucleotide Repeat Expansion
(genetics)
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