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Different genetic features associated with colon and rectal carcinogenesis.
- Source :
-
Clinical cancer research : an official journal of the American Association for Cancer Research [Clin Cancer Res] 2004 Jun 15; Vol. 10 (12 Pt 1), pp. 4015-21. - Publication Year :
- 2004
-
Abstract
- Purpose: The issue of whether colon and rectal cancer should be considered as a single entity or two distinct entities is still debated, and there is a need to improve studies addressing the heterogeneity of the pathogenetic pathway leading to sporadic colorectal cancers (SCRCs) as well as to identify biological and/or molecular differences between colon and rectal cancers.<br />Experimental Design: Specimens of SCRCs were analyzed for somatic mutations in APC, K-ras, and TP53 genes and loss-of-heterozygosity of chromosome 18.<br />Results: Eleven SCRCs showed microsatellite instability. APC mutation frequency was significantly lower in microsatellite instability (MIN+) than in MIN- SCRCs. All MIN- SCRCs showed beta-catenin overexpression. A combined analysis of the biomarkers revealed two pathways mainly represented by MIN- SCRCs and differently followed on the basis of tumor location, APC-K-ras-TP53-Ch18q and APC-TP53-Ch18q.<br />Conclusions: The APC-beta-catenin pathway is inactivated in MIN- SCRCs and represents the first hit of SCRC development. Two preferential pathways followed by SCRCs occur, one K-ras dependent, in agreement with the Fearon and Vogelstein model, and the other K-ras independent. Significant differences between colon and rectal tumors occur in our series of MIN- SCRCs. The different pathways observed and their distribution can be summarized as follows: (a) K-ras mutations were more commonly detected in colon than in rectum; (b) the number of mutations detected was significantly higher in colon than in rectal tumors; and (c) a mutational pattern restricted to the APC gene was more common in rectal than in colon tumors. This molecular characterization can be translated into a clinical setting to improve diagnosis and to direct a rationale pharmacological treatment.
- Subjects :
- Aged
Biomarkers, Tumor
Cytoskeletal Proteins metabolism
DNA Mutational Analysis
Exons
Female
Genes, APC
Genes, p53
Genes, ras genetics
Humans
Immunohistochemistry
Loss of Heterozygosity
Male
Microsatellite Repeats
Middle Aged
Trans-Activators metabolism
beta Catenin
Chromosomes, Human, Pair 18
Colonic Neoplasms genetics
Mutation
Rectal Neoplasms genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1078-0432
- Volume :
- 10
- Issue :
- 12 Pt 1
- Database :
- MEDLINE
- Journal :
- Clinical cancer research : an official journal of the American Association for Cancer Research
- Publication Type :
- Academic Journal
- Accession number :
- 15217933
- Full Text :
- https://doi.org/10.1158/1078-0432.CCR-04-0031