Loss of Heterozygosity Identifies Multiple Sites of Allelic Deletions on Chromosome 1 in Human Male Germ Cell Tumors
Chromosomes, Human, Pair 1
Cytogenetic analysis of human male germ cell tumors (GCTs) and derived cell lines revealed frequent deletions and rearrangements of chromosome 1. However, no detailed molecular analysis of these aberrations has thus far been performed. We undertook loss of heterozygosity (LOH) analysis utilizing a panel of 48 GCTs at 22 subregionally mapped polymorphic loci on both arms of chromosome 1. Eight probes, for which precise mapping data were unavailable, were subregionally mapped to specific regions by fluorescence in situ hybridization. Allelic losses were observed in 46% of cases on 1p and in 23% of cases on 1q. Teratomas showed higher frequency of allelic losses compared to embryonal carcinomas, yolk sac tumors, and seminomas, consistent with the results of our previous allelotype analysis, which showed overall higher genetic loss in teratomas compared to embryonal carcinomas. Our LOH study of chromosome 1 identified 4 sites of frequent deletions, 3 in the short arm (1p13, 1p22, and 1p31.3-32.2) and 1 in the long arm (1q32). Of these, 38.5% LOH at 1p22 (D1S16) identifies the site of a novel candidate tumor suppressor gene (TSG), possibly associated with GCTs. LOH at the remaining sites (1p13, 1p31.3-32.2, and 1q32) has also been reported in breast carcinomas, suggesting the involvement of TSGs common to both tumor types.