Microsatellite instability in tumor and nonneoplastic colorectal cells from hereditary non-polyposis colorectal cancer and sporadic high microsatellite-instable tumor patients

Genetic alterations such as loss of heterozygosity (LOH) and microsatellite instability (MSI) have been frequently studied in various tumor types. Gen etic heterogeneity of nonneoplastic cells has not yet been sufficiently inv estigated. However, genomic instability in normal cells could be a potentia lly important issue, in particular when these cells are used as reference i n LOH and MSI analyses of tumor samples. in order to investigate possible g enetic abnormalities in normal cole rectal cells of tumor patients, MSI ana lyses of normal colonic mucosa were performed. Up to 15 different laser-mic rodissected normal regions containing 50-150 cells were investigated in eac h of 15 individual microsatellite-stable, sporadic high microsatellite-inst able (MSI-H) and hereditary non-polyposis coli cancer (HNPCC) colorectal ca ncer patients. Frequent MSI and heterogeneity in the MSI pattern were found both in normal and tumor cells from 10 HNPCC and sporadic MSI-H tumor pati ents whose tumors had defect mismatch repair protein expressions. This obse rvation shows that MSI can also occur in nonneoplastic cells which has to b e considered in MSI analyses for molecular HNPCC screening. In addition, co nsiderable genetic heterogeneity was detected in all MSI-H (sporadic and HN PCC) tumors when analyzing five different regions with less than 150 cells, respectively. These differences were not detectable in larger tumor region s containing about 10,000 cells. Thus, heterogeneity of the MSI pattern (e. g. intratumoral MSI) is an important feature of tumors with the MSI-H pheno type. Copyright (C) 2001 S. Karger AG, Basel.