title: Uniparental origin of i(12p) in human germ cell tumors.
abstract: 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.
authors.affiliation: Department of Human Genetics, University Hospital, Nijmegen, The Netherlands.
authors.forename: R J
authors.initials: RJ
authors.lastname: Sinke
authors.forename: R F
authors.initials: RF
authors.lastname: Suijkerbuijk
authors.forename: B
authors.initials: B
authors.lastname: de Jong
authors.forename: J W
authors.initials: JW
authors.lastname: Oosterhuis
authors.forename: A
authors.initials: A
authors.lastname: Geurts van Kessel
mesh_terms: D002869:Chromosome Aberrations; D002881:Chromosomes, Human, Pair 12 / Q000648:ultrastructure*; D005819:Genetic Markers; D006801:Humans; D008957:Models, Genetic; D009373:Neoplasms, Germ Cell and Embryonal / Q000235:genetics*; D010290:Parents; D012150:Polymorphism, Restriction Fragment Length
chemical_list: D005819:Genetic Markers