Microsatellite alterations and K-ras, TGF beta RII, IGFRII and bax mutations in sporadic cancers of the gastrointestinal tract

DNA was analyzed from 57 sporadic gastrointestinal tumors (34 pancreatic ca ncers, 23 colon tumors) and cognate normal tissues to verify whether mutati ons at coding sequences were associated with microsatellite instability (MS I). Genomic instability was present in 41% (14134) of pancreatic samples an d in 26% (6/23) of colon cancers previously tested by six microsatellite ma rkers. The tumors included 37 cases showing no MSI; 15 cases with MSI at on ly 1 locus and 5 cases with MST at 2 or more loci. All the samples were scr eened for mutations in genes containing repeated tracts in their coding seq uences (TGF beta RII, IGFRII and bax) and in codon 12 of the K-ras oncogene . Furthermore, loss of heterozygosity (LOH) at NM23.H1 locus was tested, 17 /34 (50%) pancreatic tumors and 6/23 (26%) colon cancers showed mutations i n codon 12 of K-ras; allelic loss of NM23.H1 locus was found in 6/18 (33%) informative colon tumors and in no pancreatic cancers. The TGF beta RII, IG FRII and bar genes were altered in 3 (13%), 1 (4%) and 3 (13%) out of 23 co lon tumors respectively, but no mutation was detected in pancreatic cancers . Mutations in the repeated nucleotide stretches within the coding sequence s of TGF beta RII, IGFRII and bax genes were found only in colon tumors wit h a high unstable phenotype (more than 3 microsatellite loci altered).