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Publication : Modeling High-Grade Serous Ovarian Carcinoma Using a Combination of <i>In Vivo</i> Fallopian Tube Electroporation and CRISPR-Cas9-Mediated Genome Editing.

First Author  Teng K Year  2021
Journal  Cancer Res Volume  81
Issue  20 Pages  5147-5160
PubMed ID  34301761 Mgi Jnum  J:311802
Mgi Id  MGI:6780622 Doi  10.1158/0008-5472.CAN-20-1518
Citation  Teng K, et al. (2021) Modeling High-Grade Serous Ovarian Carcinoma Using a Combination of In Vivo Fallopian Tube Electroporation and CRISPR-Cas9-Mediated Genome Editing. Cancer Res 81(20):5147-5160
abstractText  Ovarian cancer is the most lethal gynecologic cancer to date. High-grade serous ovarian carcinoma (HGSOC) accounts for most ovarian cancer cases, and it is most frequently diagnosed at advanced stages. Here, we developed a novel strategy to generate somatic ovarian cancer mouse models using a combination of in vivo electroporation and CRISPR-Cas9-mediated genome editing. Mutation of tumor suppressor genes associated with HGSOC in two different combinations (Brca1, Tp53, Pten with and without Lkb1) resulted in successfully generation of HGSOC, albeit with different latencies and pathophysiology. Implementing Cre lineage tracing in this system enabled visualization of peritoneal micrometastases in an immune-competent environment. In addition, these models displayed copy number alterations and phenotypes similar to human HGSOC. Because this strategy is flexible in selecting mutation combinations and targeting areas, it could prove highly useful for generating mouse models to advance the understanding and treatment of ovarian cancer. SIGNIFICANCE: This study unveils a new strategy to generate genetic mouse models of ovarian cancer with high flexibility in selecting mutation combinations and targeting areas.
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