Genetic pathways in the evolution of morphologically distinct colorectal neoplasms.

作者: Carethers Jm , Laghi L , Yashiro M , Boland Cr , Slezak P

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摘要: Colorectal adenomas can be morphologically classified as exophytic or flat. Polypoid cancers and arising de novo (ie., without any adenomatous component) might the results of genetic progression from flat adenomas, respectively. In this study, we examined 94 distinct neoplastic specimens for mutations in K-RAS analyzed 10 microsatellite loci tightly linked to tumor suppressor genes APC, p53, DCC/SMAD4, hMSH2, hMLH1. were significantly associated with [11 21 (52%)] compared [2 13(15%), P < 0.03] polypoid [17 25 (68%)] [7 (28%), 0.01]. Two cancer cases demonstrated three four different mutations, respectively, suggesting multiple areas clonal expansion. Cancers loss heterozygosity (LOH) at chromosome 3p pol ypoid [6 18(33%) versus 1 20(5%), 0.03], whereas prevalence LOH chromosomes 2p, 5q, 17p, 18q instability not between groups. For all cancers, 17p occurred 47 51%, However, 0 16% benign lesions, their role malignant transformation. There was no difference lesions. These findings suggest that (a) mutant is growth colonic neoplasms, (b) some colorectal lose during evolution, which seen cancers. Half near transition lesions reported previously, irrespective morphology. may more than one avenue formation, correlates morphological characteristics.

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