Modeling High-Grade Serous Ovarian Carcinoma Using a Combination of In Vivo Fallopian Tube Electroporation and CRISPR-Cas9-Mediated Genome Editing.

Autor:	Teng K; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada.; Department of Human Genetics, McGill University, Montreal, Canada., Ford MJ; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada.; Department of Human Genetics, McGill University, Montreal, Canada., Harwalkar K; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada.; Department of Human Genetics, McGill University, Montreal, Canada., Li Y; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada.; Department of Human Genetics, McGill University, Montreal, Canada., Pacis AS; Canadian Centre for Computational Genomics, McGill University, Montreal, Canada., Farnell D; Department of Pathology, Laboratory Medicine, University of British Columbia, Vancouver, British Columbia.; Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, British Columbia., Yamanaka N; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada., Wang YC; Department of Human Genetics, McGill University, Montreal, Canada.; McGill University and Genome Centre, Montreal, Canada., Badescu D; Department of Human Genetics, McGill University, Montreal, Canada.; McGill University and Genome Centre, Montreal, Canada., Ton Nu TN; Department of Pathology, McGill University Hospital Research Institute, Montreal, Canada., Ragoussis J; Department of Human Genetics, McGill University, Montreal, Canada.; McGill University and Genome Centre, Montreal, Canada.; Department of Bioengineering, McGill University, Montreal, Canada., Huntsman DG; Department of Pathology, Laboratory Medicine, University of British Columbia, Vancouver, British Columbia.; Department of Molecular Oncology, BC Cancer Research Institute, Vancouver, British Columbia., Arseneau J; Department of Pathology, McGill University Hospital Research Institute, Montreal, Canada., Yamanaka Y; Rosalind and Morris Goodman Cancer Research Centre, McGill University, Montreal, Canada. yojiro.yamanaka@mcgill.ca.; Department of Human Genetics, McGill University, Montreal, Canada.
Jazyk:	angličtina
Zdroj:	Cancer research [Cancer Res] 2021 Oct 15; Vol. 81 (20), pp. 5147-5160. Date of Electronic Publication: 2021 Jul 23.
DOI:	10.1158/0008-5472.CAN-20-1518
Abstrakt:	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. (©2021 The Authors; Published by the American Association for Cancer Research.)
Databáze:	MEDLINE
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