[Analysis of K-ras, BRCA1/2, CHEK2 mutations and microsatellite markers (loss of heterozygosity at 9p, 17p and 18q) in sporadic pancreas adenocarcinomas].

The purpose of this study was to investigate informativety and clinical significance of most frequent somatic alterations in K-ras, TP53, CDKN2A, MADH4 and more uncommon mutations in BRCA1, BRCA2, CHEK2 genes, which arise on preinvasive stage in sporadic pancreatic adenocarcinomas (PA), in Russian patients. We examined surgically resected and manually microdissected primary PA tissue samples and samples of normal pancreatic tissue for 37 individuals. K-ras mutations in codon 12 were found in 24 tumors (0.65) and none of normal tissue samples. No mutations were detected in BRCA1(185delAG, 300T > G, 4153delA, 4158A > G,5382insC), BRCA2 (695insT, 6174delT) and CHEK2 (1100delC) genes. Informativety for allelic loss of three tumor suppressor genes studied had not statistically significant differences: 60% - for TP53 (GDB186817) and CDKN2A (D9S974 + D9S162); and 65.7% - for MADH4 (D18S363 + D18S474) (t = 0.48). Maximal frequency of loss of heterozygosity (LOH) was observed for CDKN2A - 0.95. For TP53 and MADH4 it was 0.62 and 0.70 respectively. The tumors included 80% cases showing LOH on different chromosomal loci. The combination of K-ras mutations (c.12) and LOH at 9p, 17p and 18q resulted in a high informativety of selected molecular markers: 85.7%. Instability of microsatellites was found only in 9% of PA.