A comprehensively characterized cell line panel highly representative of clinical ovarian high-grade serous carcinomas
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Kelsie L. Thu1,*, Mahboubeh Papari-Zareei2,*, Victor Stastny2, Kai Song2,3, Michael Peyton2, Victor D. Martinez1, Yu-An Zhang2, Isabel B. Castro4, Marileila Varella-Garcia4, Hanquan Liang5, Chao Xing5, Ralf Kittler5,6, Sara Milchgrub7, Diego H. Castrillon8, Heather L. Davidson9, C Patrick Reynolds9, Wan L. Lam1, Jayanthi Lea10 and Adi F. Gazdar11
1British Columbia Cancer Agency Research Centre and University of British Columbia, Vancouver, BC, Canada
2Hamon Center for Therapeutic Oncology Research, UT Southwestern Medical Center, Dallas, TX, USA
3School of Chemical Engineering and Technology, Tianjin University, Tianjin, P.R. China
4Division of Medical Oncology, University of Colorado Denver School of Medicine, Aurora, CO, USA
5Eugene McDermott Center for Human Growth & Development, UT Southwestern Medical Center, Dallas, TX, USA
6Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
7Department of Pathology, UT Southwestern Medical Center, Dallas, TX, USA
8Department of Pathology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
9Cell Biology & Biochemistry, Internal Medicine, and Pediatrics, School of Medicine Texas Tech University Health Sciences Center, Lubbock, TX, USA
10Obstetrics & Gynecology, UT Southwestern Medical Center, Dallas, TX, USA
11Hamon Center for Therapeutic Oncology Research, Department of Pathology and Simmons Comprehensive Cancer Center, UT Southwestern Medical Center, Dallas, TX, USA
*These authors have contributed equally to this work
Adi F. Gazdar, email: email@example.com
Keywords: high-grade serous ovarian carcinoma, cell models, patient-derived xenograft, exome-sequencing, genomic characterization
Received: November 14, 2015 Accepted: May 22, 2016 Published: June 10, 2016
Recent literature suggests that most widely used ovarian cancer (OVCA) cell models do not recapitulate the molecular features of clinical tumors. To address this limitation, we generated 18 cell lines and 3 corresponding patient-derived xenografts predominantly from high-grade serous carcinoma (HGSOC) peritoneal effusions. Comprehensive genomic characterization and comparison of each model to its parental tumor demonstrated a high degree of molecular similarity. Our characterization included whole exome-sequencing and copy number profiling for cell lines, xenografts, and matched non-malignant tissues, and DNA methylation, gene expression, and spectral karyotyping for a subset of specimens. Compared to the Cancer Genome Atlas (TCGA), our models more closely resembled HGSOC than any other tumor type, justifying their validity as OVCA models. Our meticulously characterized models provide a crucial resource for the OVCA research community that will advance translational findings and ultimately lead to clinical applications.
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