Spectrum of germ-line MLH1 and MSH2 mutations in Austrian patients with hereditary nonpolyposis colorectal cancer.

摘要: BACKGROUND: Germ-line mutations in mismatch repair genes are associated with the hereditary nonpolyposis colorectal cancer (HNPCC) syndrome, which is characterized by susceptibility to of colon, endometrium, small bowel or urothelium at an unusually young age and a high degree penetration all generations. MATERIAL AND METHODS: One hundred nine individuals from 46 Austrian families who fulfilled Amsterdam criteria (n = 29) least one Bethesda guidelines (n= 17) were analyzed for MLH1 MSH2. Microsatellite instability was determined tumors index persons affected relatives. RESULTS CONCLUSION: High-grade present 60.6% tumor samples patients. Twenty-three germ-line DNA sequence variants 24/46 four somatic three detected Fifteen novel. None newly identified found 100 alleles healthy control individuals. We able characterize two intronic (MLH1 c.589-10T > A; MSH2 c.367-1G A) regard their effect on mRNA. Both created new splice sites that replaced regular ones. occurred 44.8% fulfilling 35.3% The detection pathogenic mutation strongly correlated microsatellite (p 0.007). This study first comprehensive report patients HNPCC.