CRISPR/Cas9-derived models of ovarian high grade serous carcinoma targeting Brca1, Pten and Nf1, and correlation with platinum sensitivity.

ABSTRACT: Transplantable murine models of ovarian high grade serous carcinoma (HGSC) remain an important research tool. We previously showed that ID8, a widely-used syngeneic model of ovarian cancer, lacked any of the frequent mutations in HGSC, and used CRISPR/Cas9 gene editing to generate derivatives with deletions in Trp53 and Brca2. Here we have used one ID8 Trp53 ^-/- clone to generate further mutants, with additional mutations in Brca1, Pten and Nf1, all of which are frequently mutated or deleted in HGSC. We have also generated clones with triple deletions in Trp53, Brca2 and Pten. We show that ID8 Trp53 ^-/-;Brca1 ^-/- and Trp53 ^-/-;Brca2 ^-/- cells have defective homologous recombination and increased sensitivity to both platinum and PARP in

SUBMITTER: Walton JB 

PROVIDER: S-EPMC5715106 | biostudies-literature | 2017 Dec

REPOSITORIES: biostudies-literature