Altered dosage of the sex chromosomes in human testicular cancer: A molecular genetic study

Thirty‐one males with testicular germ‐cell tumors were studied by Southern hybridization using X‐ and Y‐chromosome‐specific probes as well as a pseudoautosomal probe. Densitometric analysis showed changes in the relative dosage of Y‐chromosomal fragments in tumor DNA from 12 out of 31 patients (39%) as compared to normal DNA from the same patients. In 11 tumors the relative intensity ratios of Y‐chromosome‐specific fragments had decreased from the normal value of I to values between 0 and 0.77. An increase in the Y‐chromosomal dosage was observed in I case. The entire Y chromosome was apparently involved in most patients but 2 tumors revealed regional variation. Tumor DNA of 2 patients with Y‐chromosomal deficiency showed a concomitant increase in the X chromosomal dosage. The pseudoautosomal region that is shared by both sex chromosomes was involved in a total of 8 tumors (26%), 2 of which did not show any obvious dosage changes with probes detecting strictly X‐ or Y‐chromosome‐specific fragments. Autosomal alterations in the present tumor series have been described. A dosage change involving the sex chromosomes accompanied loss of heterozygosity at loci in 3p or lip in 10 tumors out of 15 (67%). Seminomas tended to be affected more often than non‐seminomas by either type of alteration. Our results indicate that changes in the sex chromosomes occur in a substantial proportion of male germ‐cell tumors and, together with other defects, may constitute an important step in tumor development and/or progression.