Different genetic features associated with colon and rectal carcinogenesis.
Clin Cancer Res
; 10(12 Pt 1): 4015-21, 2004 Jun 15.
Article
en En
| MEDLINE
| ID: mdl-15217933
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. EXPERIMENTALDESIGN:
Specimens of SCRCs were analyzed for somatic mutations in APC, K-ras, and TP53 genes and loss-of-heterozygosity of chromosome 18.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.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.
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Bases de datos:
MEDLINE
Asunto principal:
Neoplasias del Recto
/
Cromosomas Humanos Par 18
/
Neoplasias del Colon
/
Mutación
Tipo de estudio:
Prognostic_studies
/
Risk_factors_studies
Límite:
Aged
/
Female
/
Humans
/
Male
/
Middle aged
Idioma:
En
Revista:
Clin Cancer Res
Asunto de la revista:
NEOPLASIAS
Año:
2004
Tipo del documento:
Article
País de afiliación:
Italia