Microsatellite instability and frameshift mutations in the bax gene in hereditary nonpolyposis colorectal carcinoma

We studied microsatellite instability (MI) and box gene abnormalities in co lorectal carcinomas from 36 patients diagnosed as having hereditary nonpoly posis colorectal cancers (HNPCC) according to the clinical criteria (12 wit h confirmed HNPCC in group A and 24 at high risk of HNPCC in group B) and f rom 20 randomly selected patients with other colorectal cancers. MI was exa mined at 4 dinucleotide microsatellite loci and one mononucleotide locus, F rameshift mutations in the bar gene were detected by polymerase chain react ion-single strand conformation polymorphism analysis, MI was detected in 7 of the 12 patients in group A and 12 of the 24 in group B, Three MI pattern s were identified: type 1, MI in both mono- and dinucleotide repeats; type 2, MI only in mononucleotide repeats and type 3, MI only in dinucleotide re peats, Most MI-positive patients in group A showed type 1 MI, whereas in gr oup B, 5 showed type 1, 3 showed type 2 and 4 showed type 3, Frameshift mut ations in the bax gene correlated strongly with type. 1 and type 3 MI. Thes e results indicate that mutations of different DNA mismatch repair genes ma y cause several types of MI and result in several different clinical phenot ypes of HNPCC. The bax gene may be one of the target genes which play a rol e in the tumorigenesis of HNPCC.