Genetic alterations in chronic pancreatitis: evidence for early occurrence of p53 but not K-ras mutations.

Abstract

In patients suffering from chronic pancreatitis the risk for the development of pancreatic cancer ranges from 4 to 6 per cent. Various mutations are associated with pancreatic cancer, especially of p53 and K-ras. The incidence of these mutations in resected chronic pancreatitic tissue was investigated. In the present study DNA from 80 samples of tissue from patients with chronic pancreatitis was isolated and subjected to single-strand conformation polymorphism (SSCP) analysis of p53 exons 5-9 and restriction fragment length polymorphism analysis of K-ras (codon 12). No mutations in the K-ras gene were detected. On SSCP analysis, eight of 80 cases of chronic pancreatitis showed alterations (two in exon 5, four in exon 6, two in exon 7). DNA sequence analysis revealed one deletion of 21 amino acids (exon 5), four polymorphisms in exon 6 with no change in the amino acid sequence, one point mutation in exon 5, and two point mutations located in the intron between exons 6 and 7. These data show that in some cases of chronic pancreatitis mutations in the p53 gene occur without morphological evidence of pancreatic cancer.