Detection of microsatellite instability in peripheral blood of a Filipino family with HNPCC
One approach in genetic screening of families with suspected HNPCC is to test a tumor tissue sample for a characteristic called "microsatellite instability" (MSI) before considering mutation analysis. Whether MSI can be detected in HNPCC carriers before tumor diagnosis is not clear. The aim of this study is to establish a presymptomatic diagnosis based on analysis of microsatellite instability. Peripheral blood was obtained from 26 members of a Filipino family with HNPCC (Amsterdam II criteria). Ten members of a non-HNPCC family posed as control. DNA was extracted and PCR was performed using the five Bethesda panel of markers as primers. Single strand conformation polymorphism (SSCP) was used to detect sequence difference between nucleic acid samples. Five members of the family showed MSI in four markers, twelve were positive for alteration in 3 markers, seven members in 2 markers and only 2 were unstable in 1 marker. Six members of the HNPCC family were already diagnosed with cancer prior to blood and collection and all were found to have MSI in 3-4 markers. In the control family, all members had MSI score ranging from 0-2 for the 5 Bethesda markers. Sixteen HNPCC members found with MSI-H were also positive for mutation in either in hMLH1 and hMSH2 gene or both. Whether the MSI status of HNPCC members without tumors will be predictive of their clinical progression remains to be studied.