Molecular studies of the sex chromosomes in human testicular cancer: pronounced changes in X and Y chromosome dosage in some tumors.

Nine males with testicular germ cell tumors were studied by Southern blotting using probes recognizing different regions of the X and Y chromosomes. In the tumors of three patients, an imbalance was noted with a relative deficiency of DNA of Y-chromosomal and a concurrent excess of that of X-chromosomal origin. The X:Y signal ratios were 4, 4, and 2, respectively, in tumor DNA relative to normal DNA, and the ratios of Y to an autosomal locus were 0.4, 0.6, and 0.7, respectively, in the same tumors. Several loci on both arms of the Y chromosome were similarly involved. No structural abnormalities of Y chromosome DNA could be demonstrated. The X/Y change occurred in two of the three patients with nonseminomatous tumors and in two of the three patients with metastatic disease. To account for the results, two alternative models are discussed: first, loss of the Y chromosome and increase in X chromosome number in some but not all tumor cells; second, polyploidization with one Y chromosome and several X chromosomes.