Alterations of K-ras and p53 mutations in colorectal cancer patients in Central Europe

Many molecular investigations of colorectal cancer (CRC) have suggested tha t the accumulation of specific mutations in proto-oncogenes and tumor suppr essor genes regulating cell growth via signal transduction trigger the stag ewise progression to malignancy. In this study, the frequency, location, an d type of mutations of the K-ras proto-onco gene exon 1 and p53 tumor suppr essor gene exons 5-8 were analyzed in colorectal carcinomas of 65 patients from Central Europe, using polymerase chain reaction (PCR)-cold single-stra nd conformation polymorphism (SSCP) screening and direct sequencing. The in cidence of K-ras activating mutations in these Central European samples was lower (25%) compared to that obtained in American and western European pop ulations (40-50% at least), while the incidence of p53 inactivating mutatio ns was similar (58%). These results suggest that some other genetically lin ked mechanisms may play a role in CRC development and progression, and henc e K-ras and p53 mutations cannot be considered to be universal genetic mark ers for CRC.