GENETIC EVENTS IN SPORADIC COLORECTAL ADENOMAS - K-RAS AND P53 HETEROZYGOUS MUTATIONS ARE NOT SUFFICIENT FOR MALIGNANT PROGRESSION

Twenty-four sporadic colorectal adenomas were analysed for the presenc e of allelic loss on the short arm of chromosome 17 as well as mutatio ns in the K-ras and p53 genes. Chromosome 17p13 allelic loss was not p resent in 14 out of 14 informative cases. K-ras mutations were observe d in 15 out of 24 cases. A p53 gene mutation (GGC --> GAC at codon 245 ) was detected in two biopsies taken at a four year interval from a re current rectal villous adenoma. Both biopsies also contained the same K-ras gene mutation (GGT --> GTT at codon 12). The data from the recur rent rectal adenoma provide in vivo evidence that K-ras and p53 hetero zygous mutations confer a proliferative advantage but together are not sufficient for malignant transformation.