Grant: Operating Grant - PA: Regional Partnership Program - Newfoundland and Labrador

Major contributions to our understanding of cancer susceptibility genes have come from investigations of families that show genetic heritability for specific cancers. Genes that confer cancer susceptibility play a particularly important role in the etiology of pediatric cancers, as they appear at a time of life when cancer risk due to environmental exposure is very low. Our ability to identify genetic determinants for cancer susceptibility may be limited if the cancer is rare in the human population. Several subtypes of ovarian cancer are more rare than the typical epithelial ovarian cancers that appear in post-menopausal women. Our research has focused on genes that contribute to spontaneous ovarian granulosa cell (GC) tumour susceptibility in female mice of a particular laboratory strain, as a model genetic system for the development of pediatric ovarian tumours that appear in infants and young girls. A genetic region on mouse Chromosome 4 and two regions on Chromosome X have been identified that confer pediatric ovarian GC tumour susceptibility in mice; furthermore, these regions are evolutionarily similar to segments of human Chromosome 1 and X. If the tumour-susceptibility genes can be identified in mice, the same genes and pathways can be further investigated in pediatric GC tumours, with the goal of successful health interventions to prolong life, preserve fertility, and ensure the long term endocrine health of infants, young girls and women who develop this subtype of ovarian cancer.