K-ras and Dpc4 mutations in chronic pancreatitis: case series.
OBJECTIVE
To assess whether alterations in the K-ras, p53, and DPC4 genes are present in pancreatitis, a potential precancerous condition that can progress to pancreatic adenocarcinoma. To investigate the alterations occurring at hot spots of K-ras (exon 1), p53 (exons 5 and 7), and DPC4 (exons 8, 10 and 11).


METHODS
In 10 patients with acute and 22 with chronic pancreatitis, without pancreatic intraepithelial neoplasia (PanIN), DNA was isolated from paraffin embedded tissue samples. The extracted DNA was analyzed by polymerase chain reaction (PCR), restriction fragment length polymorphism (RFLP) analysis, single-strand conformation polymorphism (SSCP) analysis, and DNA sequencing.


RESULTS
In acute pancreatitis samples no mutations were found in any of the investigated genes. In 7 out of 22 samples of chronic pancreatitis nucleotide substitution at exon 1 of K-ras (five at codon 12 and two at codon 13) were found. No mutations in p53 (exons 5 and 7) were detected. Two samples had nucleotide substitutions at exons 8 and 11 of DPC4, introducing STOP signal and change in the amino acid sequence, respectively. One chronic pancreatitis sample displayed simultaneous mutations in K-ras (exon 1, codon 12) and DPC4 (exon 8, codon 358).


CONCLUSIONS
Mutations of K-ras and Dpc4 genes can accumulate already in non-malignant, inflammatory pancreatic tissue, suggesting its applicability in monitoring of further destruction of pancreatic tissue and progression into malignancy.
Popović Hadzija
Marijana
M
Department of Molecular Medicine, Ruder Boskovic Institute, Zagreb, Croatia. mhadzija@irb.hr
Korolija
Marina
M
Jakić Razumović
Jasminka
J
Pavković
Pajica
P
Hadzija
Mirko
M
Kapitanović
Sanja
S
D016158:Genes, p53 / Q000235:genetics; D011905:Genes, ras / Q000235:genetics*; D006801:Humans; D009154:Mutation / Q000235:genetics*; D050500:Pancreatitis, Chronic / Q000235:genetics* / Q000473:pathology; D051901:Smad4 Protein / Q000235:genetics*
C497796:SMAD4 protein, human; D051901:Smad4 Protein