Gonadoblastoma: molecular definition of the susceptibility region on the Y chromosome

Using sequence-tagged sites we have performed deletion mapping of the Y chromosome in sex-reversed female patients with a Y chromosome and gonadoblastoma. The GBY gene (gonadoblastoma locus on the Y chromosome) was sublocalized to a small region near the centromere of the Y chromosome. We estimate the size of the GBY critical region to be approximately 1-2 Mb. Our analysis also indicates that copies of two dispersed Y-linked gene families, TSPY (testis-specific protein, Y-encoded) and YRRM (Y-chromosome RNA recognition motif) are present in all patients and that copies of TSPY but not YRRM fall within the GBY critical region as formally defined by deletion mapping. Two tumor samples showed expression of both genes and in one patient this expression was limited to a unilateral gonadoblastoma but absent in the contralateral streak gonad. Although our results do not directly implicate TSPY or YRRM in the etiology of the tumor, they raise the issue of whether there is one GBY gene in the critical region or possibly multiple GBY loci dispersed on the Y chromosome.