High-grade serous ovarian cancer induced in different sites of origin in mice exemplifies diverse features of the human disease.

Preclinical mouse models for ovarian cancer that faithfully recapitulate human disease on both histopathological and molecular levels are crucial for advancing novel interventions into the clinic. We developed three genetically engineered mouse (GEM) models for fallopian tube-originating ovarian cancer with the loss of Brca1, Trp53, and Rb expression driven by Pax8 or Ovgp1 promoters or virally induced directly in the oviductal epithelium. We profiled the tumors by histology and gene expression and compared them to a previously described ovarian cancer model derived from ovarian surface epithelium. Expression profiles from the oviductal and ovarian epithelium tumors fall within the four subtypes of human high-grade serous carcinoma (HGSC) and represent different patient subpopulations. Allograft tumor models derived from the GEMs are amenable to preclinical intervention studies and respond to standard of care therapies. These well-defined, tractable models present a valuable resource for assessing novel drugs and immunotherapies for patients with HGSC.