Replication error-type genetic instability at 1q42-43 in human male germ cell tumors

The replication error phenotype, recognized as microsatellite sequence alterations, has recently been suggested to be associated with hereditary nonpolyposis colorectal cancer and other types of sporadic tumors. We examined paired tumor-normal DNAs from 69 human male germ cell tumors for somatic instability at the 1q42-43 region. Analysis of a variable number of tandem repeats marker (D1S74) and 3 (CA)n type microsatellite loci (D1S235, D1S180, and angiotensinogen) revealed genetic alterations in tumor DNAs of 26 (38.2%) cases. The changes observed comprised rearrangements with D1S74 detected by Southern blot analysis in 4 of 55 (7%) cases; replication error-type alterations with D1S235, D1S180, and angiotensinogen in 12 of 66 (18.2%) cases; and loss of heterozygosity in 12 of 67 (17.9%) cases with the same probes. The microsatellite sequence alterations were more common in histological subsets other than teratomas, while the loss of heterozygosity was significantly more frequent in teratomas compared to other histologies. These results suggest that microsatellite instability and loss of heterozygosity at 1q42-43 may be unrelated genetic events which may play a role in germ cell tumor development.