Modeling High-grade serous ovarian carcinoma using a combination of in vivo fallopian tube electroporation and CRISPR/Cas9-mediated genome editing

In this study we generated a mouse model of high-grade serous ovarian carcinoma by targeting tumor suppressor genes Brca1, P53 and Pten using CRISPR/Cas9. The addition of Lkb1 to this combination reduced tumor latency and changed the origin of the tumor from the fallopain tube to the ovarian surface epithelium. Tumors originating the ovarian surface had distinct copy number alterations, highlighting the impact of the cell-of-origin on susceptibility and tumor development. In addition using lineage tracing and single cell RNA sequnecing techniques we investigated ovarian cancer ascities and early metastasis in the peritoneal cavity. Overall design: Whole genome sequencing of ovarian tumors and scRNA sequencing of ascties fluild isolated from a single mouse.