Spontaneous juvenile ovarian granulosa cell (GC) tumors that occur in young girls are similar to GC carcinomas that develop in SWR-derived inbred mice. We analyzed female offspring from a series of matings among SWR and SJL inbred mice for chromosomal loci underlying tumor susceptibility. Intercross F2 female mice were produced by reciprocal matings of (SWR × SJL)F1 and (SJL × SWR)F1 parents. Tumorigenesis in these F2 mice as well as in SWXJ recombinant inbred and congenic strains of mice derived from SWR and SJL showed significant (P < 0.001) association with Gct1, a dominant susceptibility locus on chromosome (CHR) 4 and with Gct2 on CHR 12. Suggestive (P < 0.01) association was found with Gct3 on CHR 15. A fourth susceptibility locus, Gct4 on CHR X, was demonstrated with a strong parent-of-origin effect associated with the paternal genotype. Imprinting and complex interactions among these four loci combine to establish the probability for GC tumorigenesis in this mouse model.
↵1 Supported by American Cancer Society Grants BE-170 and CA-62434 (to W. G. B.), GM-20919 (to E. M. E.), and CA-34196 (Cancer support to The Jackson Laboratory). The Jackson Laboratory is fully accredited by the American Association for Laboratory Animal Care.
↵2 To whom requests for reprints should be addressed, at The Jackson Laboratory, 600 Main Street, Bar Harbor, ME 04609. Phone: (207) 288-6215; Fax: (207) 288-6073; E-mail: firstname.lastname@example.org.
- Received December 23, 1997.
- Accepted June 10, 1998.
- ©1998 American Association for Cancer Research.