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. © 1993 Wiley‐Liss, Inc.