Microsatellite instability and mismatch repair gene inactivation in sporadic pancreatic and colon tumours

Genomic instability has been proposed as a new mechanism of carcinogenesis involved in hereditary non-polyposis colorectal cancer (HNPCC) and in a lar ge number of sporadic cancers like pancreatic and colon tumours. Mutations in human mismatch repair genes have been found in HNPCC patients, but their involvement in sporadic cancer has not been clarified yet. In this study w e screened 21 pancreatic and 23 colorectal sporadic cancers for microsatell ite instability by ten and six different microsatellite markers respectivel y. Microsatellite alterations were observed at one or more loci in 66.6% (1 4/21) of pancreatic cancers and in 26% (6/23) colon tumours, but all the pa ncreatic and half of the colon samples showed a low rate of microsatellite instability. All the unstable samples were further analysed for mutations i n the hMLH1 and hMSH2 genes and for hypermethylation of the hMLH1 promoter region. Alterations in the hMLH1 gene were found only in colorectal tumours with a large presence of microsatellite instability. None of the pancreati c tumours showed any alteration in the two genes analysed. Our results demo nstrate that microsatellite instability is unlikely to play a role in the t umorigenesis of sporadic pancreatic cancers and confirm the presence of mis match repair gene alterations only in sporadic colon tumours with a highly unstable phenotype.