COMPARATIVE-ANALYSIS OF MUTATIONS IN THE P53 AND K-RAS GENES IN PANCREATIC-CANCER

Mutations in codon 12 of K-ros occur in a high proportion of pancreati c cancer cases. Although there is evidence that p53 mutations also occ ur in this tumor, few studies have been reported to date and no compar ison has been made of K-ras and p53 mutations in the same tissues. Sin gle-strand conformation polymorphism and sequencing of the PCR product s were used to determine mutations in p53 gene; to detect mutations in K-ros genes, the artificial restriction fragment length polymorphism (RFLP) approach was used. Eight out of 30 tissues from primary pancrea s cancer and 3 of 4 samples from metastases showed p53 mutations. Fift een out of 17 pancreatic cancer cell lines had p53 mutations. In 2 cas es, the same p53 mutation was identified in the original tumor and in a tumor-derived cell line. The majority of p53 mutations were present in exons 5-9 of the gene. Mutations at codon 12 of the K-ras gene were identified in 23/32 pancreas cancer tissues and in 14/17 cell lines. There was no relationship between the types of mutation observed in th e 2 genes. In conclusion, mutations in K-ros and p53 genes are common in pancreatic cancer. p53 mutations may occur more frequently in metas tatic lesions than in primary tumors, although further work is necessa ry to investigate this point. (C) 1994 Wiley-Liss, Inc.