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The Role of the Mouse Y Chromosome on Susceptibility to Testicular Germ Cell Tumors

¹ Department of Genetics and Case Comprehensive Cancer Center, Case Western Reserve University, Cleveland, Ohio; ² Vascular Biology Center, Medical College of Georgia, Augusta, Georgia; and ³ Institute for Regenerative Medicine, Wake Forest University Health Sciences, Winston-Salem, North Carolina

Requests for reprints: Joseph H. Nadeau, Department of Genetics and Case Comprehensive Cancer Center, Case Western Reserve University, 10900 Euclid Avenue, Cleveland, OH 44106. Phone: 216-368-0581; Fax: 216-368-3832; E-mail: jhn4{at}case.edu.

Key Words: Sex reversal • Testicular germ cell tumors • Y chromosome

Testicular germ cell tumors (TGCT) are sex limited, occurring only in males with a Y chromosome. Recently, the gr/gr deletion on the human Y chromosome was associated with increased risk of TGCTs. In addition, the presence of Y chromosome sequences is associated with TGCTs in cases of gonadal dysgenesis. TGCTs in strain 129 males recapitulate many aspects of testicular cancer in human infants and can be used to evaluate the role of the Y chromosome in TGCT risk. We used chromosome substitution strains and a sex-reversing mutant to test the role of the Y chromosome on TGCT susceptibility. Our results show that a Y-linked gene that does not differ among the tested strains is essential for tumorigenesis. [Cancer Res 2009;69(8):3614–8]