Intratumor genetic heterogeneity in advanced human colorectal adenocarcinoma.

摘要: Colorectal carcinogenesis is widely accepted as one of the best-characterized examples stepwise progression. The existing colorectal model assumes genetic homogeneity individual tumors for main known alterations: K-ras and p53 genes point mutations loss heterozygosity (LOH) chromosome 5q 18q. object present study was to demonstrate existence an intratumor heterogeneity in advanced sporadic carcinoma these alterations. Using improved tissue microdissection DNA extraction, each tumor, amplifiable obtained from 15 20 areas, which 1 2 concerned lymph node metastases (LNM). This revealed that 10 (67%) analyzed were heterogeneous at least alteration, with between 6 genotypically different clones detected per tumor. No correlation observed genotype subclones histological differentiation or invasive propensity. Intratumor more frequently LOH than mutations, 67% 58% APC DCC locus, 20% mutation either gene. In 5 9 (56%) cases available LNM, LNM clone primary moreover, displayed a undetected conclusion, demonstrated represented topographically distinct genotypic subclones. Taking into account such significant tumors, use markers prognosis management should be reconsidered.