K-RAS AND P53 MUTATIONS IN HEREDITARY NONPOLYPOSIS COLORECTAL CANCERS

Genetic instability related to defective DNA mismatch repair genes may be involved in the pathogenesis of carcinoma in Hereditary Non-Polypo sis Colorectal Cancer (HNPCC). To test that the targets of genetic ins tability could include critical transforming genes involved in colon t umor progression, we examined 23 colorectal carcinomas in patients wit h HNPCC in order to detect somatic mutations in K-ros and p53 genes. U sing single strand conformation polymorphism followed by direct DNA se quencing, we detected 4 mutations in K-ros gene (17%) and 3 in p53 gen e (13%) which change the aminoacid sequence of the protein p53. This i s significantly lower than in sporadic cancer. Our data suggest that c olon cancer in HNPCC might partly involve a distinct pathogenetic mech anism that involves other genes than those altered in sporadic tumors. (C) 1997 Wiley-Liss, Inc,.