Analysis of microsatellite instability and BRCA1 mutations in patients from hereditary nonpolyposis colorectal cancer (HNPCC) family.

Susceptibility to colorectal cancer appears to be linked to germ-line mutations in genes causing various familial cancer syndromes. The objectives of this study were to determine microsatellite instability and the frequency of BRCA1 germ-line mutations in patients with family history of cancer. The study population consisted of 30 patients from HNPCC family. Patients completed a family history questionnaire and provided blood for mutation analysis. Seven out of 30 investigated samples (23%) were found to be MSI-positive, 6 MSI-high and 1 MSI-low. Ex20insC and ExII17delA mutations of BRCA1 gene were identified in MSI-positive samples from HNPCC families. In the present study one Ex20insC mutation and two ExII17delA mutations were detected only in MSI-high samples. Genetic alterations seem to be a risk factor of colorectal cancer in subjects belonging to HNPCC families with high incidence of this cancer. The lack of detectable germ-line mutations in most cases suggests that there are probably additional, as yet unidentified genes predisposing to this disease.