engleski

Gene mutations as biomarkers in chronic pancreatitis

Pancreatitis is an inflammatory disease characterized by tissue destruction. The histological changes in acute pancreatitis usually revert to normal, but irreversible changes in chronic pancreatitis could lead to malignancy. We assumed that alterations more than one gene might be associated with pancreatitis. Therefore, we were getting insight into alterations occurring at hot spots of K-ras (codons 12, 13), p53 (codons 175, 248) and DPC4 (codons 358, 412, 539). DNA was isolated from 10 acute and 22 chronic paraffin embedded pancreatitis tissue samples without pancreatic intraepithelial neoplasia, and subjected to SSCP, RFLP and DNA sequencing. Not one sample of acute pancreatitis displayed mutations in any investigated gene. Seven samples of chronic pancreatitis showed nucleotide substitution in exon 1 of K-ras. No mutations in p53 were detected. Two samples revealed nucleotide substitutions in exons 8 and 11 of DPC4, introducing STOP signal and change in the amino acid sequence, respectively. It is worth mentioning one chronic pancreatic sample that displayed simultaneous mutations in K-ras (codon 12) and DPC4 (codon 539). These results show that mutations of K-ras and DPC4 can be accumulated already in non-malignant pancreatic tissue, suggesting its applicability in monitoring of further destruction of pancreatic tissue and progression into malignancy.

Pancreatitis; K-ras; p53; DPC4

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