K-RAS MUTATION IN GREEK PATIENTS WITH POORLY AND MODERATELY DIFFERENTIATED TUMORS OF THE LOWER INTESTINAL-TRACT

The K-ras protooncogene is activated via mutations in approximately 40 % of primary colorectal adenocarcinoma. This finding suggests that the se genetic alterations. are important events in the genesis of colon c ancer and should be correlated with other parameters in order to infer some conclusions relevant to the etiology and the pathogenesis of thi s type of cancer. In our study we examined whether the incidence of K- ras mutations detected in 23 samples with colorectal adenocarcinomas, was related to different anatomical sites within the lower intestinal tract (transverse colon, descending colon and rectosigmoid region) and also the correlation between K-ras mutations and depth of invasion, l evel of tumour cell differentiation and metastasis to the regional lym ph nodes. For this study the critical regions for the activation of th e K-ras protooncogene were amplified by the PCR technique and the part icular sequences analysed after their membrane transfer, by differenti al hybridization with selected synthetic oligonucleotides. Our results demonstrated that 39% of the adenocarcinomas examined contained point mutations, and 66.6% of these were located in the second position of K-ras codon 12 whereas the other 33.3% were located in the second posi tion of codon 13. 77.8% of the mutations were located at the rectosigm oid region and the relevance of the mutations was higher in poorly dif ferenciated tumours. The depth of invasion was associated with the pre sence of a mutation whereas no correlation was found between the prese nce of a mutation anb the regional lymph node metastasis.