Approaches to identification of HNPCC suspected patients in Slovak population

Patients with hereditary non-polyposis colorectal cancer (HNPCC) have a DNA mismatch repair defect (MMR) in their tumor tissue that results in instabi lity of microsatellite DNA sequences (MSI). Thus, MSI analysis may effectiv ely indicate this form of cancer that should be then proved by analysis of germline mutations in MMR genes. The aim of this study was to identify HNPC C suspected patients in the Slovak population by investigating microsatelli te instability in colorectal tumor tissues. MSI was studied at 5-11 loci in matched tumor and normal DNA using radioactively labeled PCR products sepa rated on sequencing gels. High microsatellite instability (MSI-H) was prese nt only in patients younger than 50 years, in 100% of patients having two a ffected relatives by colorectal cancer and in 67% of patients with only one affected relative. Tn both groups of patients colorectal cancer was presen t in two successive generations. No MSI-H was found in the group of patient s older than 50 years, even if they had positive family history for colorec tal cancer. Among all markers used, the BAT26 mononucleotide repeat (100%), D10S197 and D13S175 (62.5%) dinucleotide repeats were the most frequently altered ill the tumor tissues. Retrospective analysis revealed that some of the patients having MSI-H tumors have had clinicopathological characterist ics frequently reported to HNPCC. The family members of those patients with MST-H are enrolled in preventive health care program until mutational anal yses will enable to select carriers from non-carriers of mutated MMR genes.