MUTATED C-K-RAS IN SMALL PANCREATIC ADENOCARCINOMAS

The objective of this study was to determine whether small human pancreatic adenocarcinomas contain activated c-K-ras as an approach to answering the question of whether c-K-ras mutation is an early change in this disease. Eight pancreatic adenocarcinomas in the range 1.2-3 cm were analyzed for c-K-ras mutation at codon 12 by amplifying the c-K-ras gene around codon 12 out of paraffin-embedded tissue sections using the polymerase chain reaction. c-K-ras mutations were detected by allele-specific oligonucleotide hybridization. Six of the eight small pancreatic adenocarcinomas contained mutated c-K-ras at codon 12, position 2, and two of the six tumors had an additional mutation at position 1 of codon 12. Our results indicate that small pancreatic adenocarcinomas are similar to large, late-stage pancreatic adenocarcinomas in that 75% of the tumors analyzed contain mutated c-K-ras at codon 12, position 2. These data suggest that c-K-ras mutation occurs early and may therefore have a role in initiation of human pancreatic adenocarcinoma.