Microsatellite instability in germ cell tumors of the testis and ovary

Objectives. Widespread replication-type error (RER) is a genetic alteration that has been observed in many different neoplasms and has been associated with defective DNA repair activity. There are conflicting data regarding t he role that this type of genetic instability plays in the development and progression of adult germ cell tumors. Methods. Universal amplification was performed on 104 paired specimens of t umor and constitutional DNA isolated from adult male and female germ cell t umors, in addition to subpopulations of carcinoma in situ (CIS), the precur sor of testicular germ cell tumors (TGCTs). Preamplified DNA samples of TGC Ts and ovarian germ cell tumors (OGCTs) were assayed for the presence of RE R at 78 and 64 microsatellite loci, respectively. Results. RER was observed at a single microsatellite locus in 7 of 24 indiv idual testicular germ cell tumors, including subpopulations of CIS isolated from one of these patients. There was some evidence of RER clustering for microsatellite loci mapping to the short arm of chromosome 12. Genetic inst ability was more frequent in OGCTs, with widespread RER observed at 38 of 6 4 microsatellite loci. These alterations were noted in 12 of 36 malignant O GCTs showing RER at 1 of more loci, including 3 OGCTs demonstrating RER at more than 6 separate microsatellite loci. Conclusions. The pathogenetic significance of genetic instability in germ c ell tumors remains uncertain, although the results of this study suggest a lesser role in TGCTs compared to that in OGCTs. (C) 2000 Academic Press.