AIM: Microsatellite instability (MSI) is due to defective DNA mismatch repair (MMR) and is characteristic of hereditary nonpolyposis colorectal cancer (HNPCC) tumors. The role of MSI in familial predisposition to colorectal cancer was investigated in this study by both microsatellite analysis and mutation screening of the two major MMR genes MLH1 and MSH2 among familial cases. METHODS: PCR-based microsatellite analysis was performed in blood obtained from 30 members from HNPCC families. Blood samples age matched healthy individuals (n = 28) served as control. MSI was studied at five loci containing single- or dinucleotide repeat sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12), BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12). RESULTS: MSI frequency was higher in member of HNPCC families [7/30 (23%)] than in control [3/28 (10.7%)] cases. Two MLH1 and one MSH2 mutations were identified in 7 MSI positive samples from HNPCC families. MLH1/MSH2 mutations were only in MSI high samples detected. CONCLUSION: Genetic alterations seem to be a risk factor of colorectal cancer in subjects belonged to HNPCC families with high incidence of this cancer.
AIM: Microsatellite instability (MSI) is due to defective DNA mismatch repair (MMR) and is characteristic of hereditary nonpolyposis colorectal cancer (HNPCC) tumors. The role of MSI in familial predisposition to colorectal cancer was investigated in this study by both microsatellite analysis and mutation screening of the two major MMR genes MLH1 and MSH2 among familial cases. METHODS: PCR-based microsatellite analysis was performed in blood obtained from 30 members from HNPCC families. Blood samples age matched healthy individuals (n = 28) served as control. MSI was studied at five loci containing single- or dinucleotide repeat sequences and mapping to different chromosomal locations: BAT-25 (at locus 4q12), BAT-26 (2p16), D2S123 (2p16-p21), D5S346 (5q21-q22) and D17S250 (17q11.2-q12). RESULTS: MSI frequency was higher in member of HNPCC families [7/30 (23%)] than in control [3/28 (10.7%)] cases. Two MLH1 and one MSH2 mutations were identified in 7 MSI positive samples from HNPCC families. MLH1/MSH2 mutations were only in MSI high samples detected. CONCLUSION: Genetic alterations seem to be a risk factor of colorectal cancer in subjects belonged to HNPCC families with high incidence of this cancer.