Grant: Operating Grant

In North America, ovarian cancer is the leading cause of death due to gynaecological malignancies. Ovarian cancers can be divided into subtypes based on their tumour cell types. These specific subtypes are essentially different diseases and are associated with different molecular characteristics and different prognosis. Granulosa cell tumours are one of the ovarian cancer subtypes and represent approximately 5% of all malignant ovarian tumours. For women with this disease, the success of traditional chemotherapy has been limited, suggesting the need for more effective and subtype specific treatments. We have recently shown that 95% of granulosa cell tumours have an identical mutation in a gene called FOXL2. FOXL2 is a transcription factor - a protein that regulates other genes by, turning them 'on' or 'off'. We suspect that the FOXL2 mutation found in granulosa cell tumours disrupts this regulation, which ultimately results in uncontrolled growth of granulosa cells and cancer. Our research will attempt to elucidate the specific role of FOXL2 and how a mutation in this protein contributes to granulosa cell ovarian cancer. We will firmly establish how common this mutation is in both granulosa cell tumours and also other similar tumours (sex cord-stromal tumours). In addition, through carefully designed experiments, we will determine how FOXL2 influences cell growth and whether this is altered with mutated FOXL2. We will attempt to specifically identify which genes are regulated by both the normal and mutated versions of FOXL2. Finally, we will investigate how FOXL2 participates in cellular functions involving well known signalling pathways. This research will contribute to the understanding of FOXL2 and its role in granulosa cell tumours. These findings could lead to the development of new therapeutics and diagnostics for granulosa cell tumours which would result in improved management and outcomes for this disease.