Grant: Travel Awards - Institute Community Support

Juvenile-onset granulosa cell (GC) tumours of the ovary represent a rare subset of sex cord-stromal tumours found in children and young women. To investigate genetic and endocrine factors that confer juvenile-type GC tumour susceptibility, we have focused on the SWR model of GC tumourigenesis. In this model, GC tumours appear spontaneously in young females with androgenic stimulation and the phenotype is heritable, with three predominant susceptibility loci on distal Chr 4 and two disparate regions of Chr X. My research centers around the investigation of gene candidates for the Granulosa cell tumour locus 6 (Gct6) mapped to 1.02 million base pairs on distal Chr X. The Gct6 locus was subject to targeted locus sequencing to identify all variants unique to the SWR genome (permissive alleles) and tumour-resistant congenic strains (suppressive alleles). A promising candidate gene for shared identity with Gct6 is the solute carrier gene Slc25a53, given empirical evidence for a unique mutation profile in mouse strains carrying permissive Gct6 alleles. Slc25a53 is a protein of the solute carrier 25a family, although it has unknown ligand specificity. Using commercially available antibodies, Slc25a53 was detected at 36kD in the normal mouse ovary using a competitive peptide and immunoblotting method. Slc25a53 was also detected in the human COV434 ovarian granulosa cell tumour cell line. The presence of Slc25a53 in the relevant cell types provides additional support for the hypothesis that Slc25a53 shares identity with Gct6 . Ongoing investigations include the temporal and sub-cellular localization of this protein (cytoplasmic vs. mitochondrial) during ovarian development and between GC tumour-permissive and tumour-resistant female mice. These investigations provide novel information about the orphan Slc25a53 protein and explore its possible connection to a rare ovarian cancer subtype.