Integrative Molecular Analysis of Murine Serous Carcinomas

Pre-clinical mouse models are used in testing and furthering our knowledge on novel treatments in various disease models. In this study, we developed genetically engineered mouse models aimed at modeling high-grade serous carcinoma found in women. These models have various combinatorial genotypes with Cre induced deletions of Brca1, Trp53, Rb1, and Nf1 (BPRN). The mouse models were found to develop tumors in the fallopian tubes and are histologically similar to high-grade serous carcinoma in women. With the targeted DNA sequencing, we showed these genetically engineered mice share similar molecular characteristics of human high-grade serous carcinoma such as acquired mutations and increased genomic instability. These findings lead us to believe the mouse model accurately depicts human high grade serous ovarian cancer both in phenotype and genotype. Thus, the BPRN mice will allow researchers to better our understanding of progression and treatment in ovarian cancer.