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Published online first on April 7, 2009
[Cancer Research, 10.1158/0008-5472.CAN-08-4881]
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0008-5472.CAN-08-4881v1
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Molecular Biology, Pathobiology, and Genetics

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

Philip D. Anderson 1, Man-Yee Lam 1, Christophe Poirier 2, Colin E. Bishop 3, and Joseph H. Nadeau 1*

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

* To whom correspondence should be addressed. E-mail: jhn4{at}case.edu.


   Abstract

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]

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







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Copyright © 2009 by the American Association for Cancer Research.