FAR LESS FREQUENT MUTATIONS IN RAS GENES THAN IN THE P53 GENE IN SKINTUMORS OF XERODERMA-PIGMENTOSUM PATIENTS

Mutations in Ha-ras, Ki-ras, and N-ras genes in squamous and basal cel l carcinomas in patients with xeroderma pigmentosum (XP) were examined by the polymerase chain reaction followed by single-strand conformati on polymorphism analysis and direct base sequencing. No mutation was d etected in codons 12, 13, and 61 of the ras genes in XP skin tumors. T his was in contrast with previous findings of a high frequency of muta tion in the p53 gene in skin tumors in XP patients. A novel mutation i n codon 6 of the Ki-ras gene was detected in a squamous cell carcinoma . The mutation was a C-->T transition at a dipyrimidine (5'-CT) sequen ce and could have been produced by solar ultraviolet light. The mutate d ras gene did not have the ability to transform NIH/ 3T3 cells. In th ree tumors, multiple base substitutions were detected in exon 1 of the Ki-ras and N-ras genes. These results and our previous work on p53 ge ne mutations suggest that mutations in ras genes are far less frequent than in the p53 gene in the skin tumors in XP patients and that ras g enes are less important in skin tumorigenesis in XP patients than is t he p53 gene. (C) 1994 Wiley-Liss, Inc.