Grant: Project Grant

Hydatidiform mole is an aberrant human pregnancy with no embryo that has fascinated scientists in all civilizations since its description by Hippocrates more than 2000 years ago. The common form of this condition affects 1 in every 600 pregnancies in western countries. Most of these moles are sporadic, not recurrent, and benign. However, up to 20% of them degenerate into malignant tumors, require single or multiple-drug chemotherapy, and may lead to the death of the patients in the absence of appropriate follow-up and treatment. Today, it is not known why some moles become malignant and not others. I, together with my team, identified a major gene, NLRP7, responsible for a rare form of recurrent moles and have made significant contribution to its current understanding. Because of the contribution of my group, patients with recurrent moles are now tested for NLRP7 and those with recessive mutations counselled that their defect lies in their oocytes and that they can have normal pregnancies and live births from ovum donation. Our most recent and important finding is that the root of this disease in patients with NLRP7 mutations stems from the placenta because it did not complete its full differentiation and that is why it keeps proliferating. This proposal aims at delineating the extent of the undifferentiated state of the placenta of recurrent moles from patients with recessive NLRP7 mutations, investigating whether the identified markers are involved in the malignant degeneration of sporadic moles, and demonstrating the roles of these markers in conferring tumorigenesis. In this application, I am seeking the CIHR support to start understanding the molecular basis of the malignant component of moles and help the most fragile patients with this condition.