Identifying the Cell of Origin for High-Grade Serous Carcinoma

Project summary

The most common and most lethal type of ovarian cancer is high grade serous carcinoma (HGSC). However we now understand that the majority of “ovarian” HGSCs originate from the fallopian tube epithelium. This discovery was critical to understand that removing the fallopian tubes from women at higher risk for developing ovarian cancer can prevent the HGSC from occurring or remove cancerous lesions before they spread to other organs. There is a significant gap in knowledge regarding the specific cell(s) of origin for HGSC. Precisely defining the epithelial cells present in the fallopian tube is critical to our understanding of HGSC pathogenesis. In this project we are looking at individual cells from normal fallopian tubes removed from patients undergoing surgery for benign indications, to determine the specific cell types and states that are present in the benign fallopian tube and in early precursor lesions. To date we have examined over 350,000 single cells from 19 patients using cutting edge technologies. We will further probe the spatial organization of fallopian tube epithelial cells and integrate our findings with those reported in the literature, comparing age and hormone-related differences in cell types in the fallopian tube, and then we will apply this knowledge to generate “maps” of the cells in the fallopian tube, determine the cell types comprising early lesions, with the overall goal of identifying the specific cell types at risk for transforming to cancer.

This grant was made possible in part by a generous donation from George and Paulette Collias in memory of Matina, Georgiana and Cindy Gatziolis.