ANALYSIS OF GENETIC ALTERATIONS IN RECTAL-CANCER - DIFFERENCES AS COMPARED WITH COLON-CANCER

Aims and methods. - We studied the mechanisms of colon and rectal carc inogenesis by analysing in a series of 83 rectal tumors the prevalence of the two tumor types characteristic of colon cancel; i.e. the LOH type, defined by p53 and APC mutations (studied by DGGE and protein t roncation assay), and the RER + type, which is characterized by the in stability of some mononucleotide repeat microsatellites (Bat 25 and Ba t26). Additionally we analyzed the occurrence of Ki-Ras mutations (dir ect sequencing). Results. - Only one tumor turned out to be RER +. Mor eover; in 59% of the tumor cases mutations were found in p53, essentia lly affecting codon 175. The APC and Ki-Ras genes were found to be mut ated in 40 and 26 % of the rectal tumors, respectively In 18 tumors (2 1 %) none of the genes studied were mutated Conclusions. - The RER + p henotype is rare among rectal tumors,,which are essentially LOH +. In these LOH + tumors the p53 gene is more frequently mutated than in col orectal tumors with the same phenotype. Mutations in the APC and Ki-Ra s genes, on the other hand, are? less frequent in rectal tumors. Tumor s with the RER- and LOH- phenotype may develop as a result of a third carcinogenesis model which must be defined.