title: Beyond genomics: critical evaluation of cell line utility for ovarian cancer research.
abstract: OBJECTIVE
  Comparisons of The Cancer Genome Atlas (TCGA) with high grade serous ovarian cancer (HGSOC) cell lines used in research reveal that many common experimental models lack defining genomic characteristics seen in patient tumors. As cell lines exist with higher genomic fidelity to TCGA, this study aimed to evaluate the utility of these cell lines as tools for preclinical investigation.
  
  
  METHODS
  We compared two HGSOC cell lines with supposed high genomic fidelity to TCGA, KURAMOCHI and OVSAHO, with the most commonly cited ovarian cancer cell line, SKOV3, which has poor genomic fidelity to TCGA. The lines were analyzed for genomic alterations, in vitro performance, and growth in murine xenografts.
  
  
  RESULTS
  Using targeted next generation sequencing analyses, we determined that each line had a distinct mutation profile, including alterations in TP53, and copy number variation of specific genes. KURAMOCHI and OVSAHO better recapitulated serous carcinoma morphology than SKOV3. All lines expressed PAX8 and stathmin, but KURAMOCHI and OVSAHO did not express CK7. KURAMOCHI was significantly more platinum sensitive than OVSAHO and SKOV3. Unlike SKOV3, KURAMOCHI and OVSAHO engrafted poorly in subcutaneous xenografts. KURAMOCHI and OVSAHO grew best after intraperitoneal injection in SCID mice and recapitulated miliary disease while SKOV3 grew in all murine systems and formed oligometastatic disease.
  
  
  CONCLUSIONS
  The research utility of HGSOC cell line models requires a comprehensive assessment of genomic as well as in vitro and in vivo properties. Cell lines with closer genomic fidelity to human tumors may have limitations in performance for preclinical investigation.
authors: Dana-Farber Cancer Institute, Boston, MA 02115, USA; Division of Gynecologic Oncology, Department of Obstetrics and Gynecology and Reproductive Biology, Brigham and Women's Hospital, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA.
authors: Kevin M
authors: KM
authors: Elias
authors: Dana-Farber Cancer Institute, Boston, MA 02115, USA; Graduate School of Arts and Sciences, Harvard University, Cambridge, MA 02138, USA.
authors: Megan M
authors: MM
authors: Emori
authors: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Eniko
authors: E
authors: Papp
authors: Dana-Farber Cancer Institute, Boston, MA 02115, USA.
authors: Emily
authors: E
authors: MacDuffie
authors: University of California Los Angeles, Jonsson Comprehensive Cancer Center, Los Angeles, CA 90095, USA.
authors: Gottfried E
authors: GE
authors: Konecny
authors: The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21287, USA.
authors: Victor E
authors: VE
authors: Velculescu
authors: Dana-Farber Cancer Institute, Boston, MA 02115, USA; Harvard Medical School, Boston, MA 02115, USA. Electronic address: rdrapkin@mail.med.upenn.edu.
authors: Ronny
authors: R
authors: Drapkin
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D005260:Female; D064593:Heterografts; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D016513:Mice, SCID; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000473:pathology*
keywords: Cell line model; Genomics; Ovarian cancer; Xenograft