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

We have developed novel genetically engineered mouse models for high-grade serous carcinoma of the ovary. We compare expression profiles of 4 different models for HGSC, one developing carcinoma from the ovarian surface epithelium (OSE) and 3 others that develop carcinoma from Fallopian tube epithelium (FTE). FTE-originating cancer models utilize either Pax8- or Ovgp1-promotor driven expression of inducible Cre recombinase (CreERT2) and the last model utilizes direct injection of adeno-virus expressing Cre recombinase into oviducts to induce the desired genetic aberrations: loss of Brca1, loss or mutation (R172H) of Trp53 and inhibition of proteins of the Rb family (via expression of K18GT121 transgene). We compare tumors from genetically engineered mouse models (GEMMs) and from GEM-derived allografts and compare them to corresponding normal tissue: ovary or oviduct (mouse equivalent of Fallopian tube). Expression profiling allowed us to investigate molecular subtypes of HGSC in these models and comparison to human HGSC.These well-defined, tractable models represent a valuable resource for assessing novel drugs and immunotherapies for patients with HGSC.