UNIPARENTAL ORIGIN OF I(12P) IN HUMAN GERM-CELL TUMORS

We present molecular data to demonstrate that the isochromosome 12p, specific for human germ cell tumors (GCTs), is of uniparental origin. Eight GCT-derived cell lines, containing one or more copies of i(12p) and/or other 12p anomalies, were analyzed with different 12p-derived polymorphic markers. The results from Ma-90, a near-diploid cell line with only one i(12p) in addition to two copies of a normal chromosome 12, clearly show an allelic 12p ratio of approximately 3:1, indicating that both 12p arms are of identical parental origin. These results were further substantiated by data obtained from the other i(12p)-positive GCT-derived cell lines. Therefore, we conclude that the i(12p) in GCTs constitutes a genuine isochromosome with genetically identical arms. The isochromosome most likely originates from a misdivision of the centromere rather than from a translocation or a non-sister chromatid exchange as proposed by others. We also found that supernumerary 12p copies, as observed in i(12p)-negative GCTs, are of uniparental origin. These observations seem to point to an important role for certain 12p-derived sequences in the development of human GCTs.