**9. Conclusions**

Recent genetic discoveries have provided profound insights into the molecular pathogenesis of ovarian SCST. As with other uncommon tumor types, insight from research of SCST will potentially be prismatic; that is, it will help clarify molecular mechanisms involved in oncogenesis. In SLCT, the discovery of DICER1 mutations highlight both the complexity and asymmetry of miRNA processing, while also

supporting the potential for 'non-coding' RNA in playing a critical role in malignant cancers. In the case of jGCT, the presence of the recurring mutations in the *gsp* oncogene and in AKT1, highlights the critical role of the cyclic AMP/protein kinase A and PI3kinase/AKT signaling pathways in hormone-mediated cell proliferation, as well as when constitutively activated, in malignancy. We and others have demonstrated that the FOXL2 C134W mutation found in aGCT would appear to be pathognomonic, however, the precise mechanism of this mutation still remains some-what controversial, despite being discovered over a decade ago. For other SCST, gene alterations and mutations appear restricted to their syndromic context. The above findings have provided insights into the biology of the respective genes involved in the pathogenesis, and to the role they play in sex-cord stromal cell development. The prognostic significance and therapeutic potential of these findings are of critical interest to those women afflicted with these malignancies. What is also very clear is that these tumors are uniquely different to the EOC, which in the context of the age of 'precision' medicine, each tumor type must be treated with a tumor-, and/or a mutation-specific approach. As an example, for the more common aGCT tumor type, advanced stage disease carries a poor prognosis, and yet, options beyond the FOXL2 mutation are still to be identified. Targeting the FOXL2 mutation is likely to be difficult. Hence further targets are potentially needed in order to treat this disease with a more targeted approach. It is clear that other genetic or genomic changes must determine late recurrence or an advanced stage. With a multi-omics approach involving the application of whole genome sequencing, whole-exome sequencing, RNA-seq as well as interrogation of the miRNA-ome, critical driver mutations for GCT or the other SCST will likely be identified, with the hope that these are 'actionable' mutations, and thus leading to more precision targeted therapy.
