K-ras gene mutations in adenomas and carcinomas of the colon.

Abstract

DNA extracted from 29 colorectal carcinomas and 40 sporadic adenomas was amplified by the polymerase chain reaction (PCR) and analysed for the presence of K-ras gene mutations at codon 12 using a panel of synthetic oligonucleotide probes specific for normal and mutated sequences. The presence of mutations was correlated with various histopathological and clinical data. Ten carcinomas (34.5%) and 14 sporadic adenomas (35%) showed K-ras mutations at codon 12. In the carcinoma group, no apparent correlation was found between the presence of mutant oncogenes and the degree of histological differentiation, Dukes' staging or the development of distant metastasis. In the adenoma group, the frequency of mutations increased with the size of the adenoma and the severity of the dysplastic changes. This study confirms that ras gene mutations are common and early events in colon carcinogenesis. They appear to give a selective growth advantage to those polyps with mutations which leads to their increase in size and thus possibly prepare the ground for malignant transformation.