title: Ovarian cancer cell line panel (OCCP): clinical importance of in vitro morphological subtypes.
abstract: Epithelial ovarian cancer is a highly heterogeneous disease and remains the most lethal gynaecological malignancy in the Western world. Therapeutic approaches need to account for inter-patient and intra-tumoural heterogeneity and detailed characterization of in vitro models representing the different histological and molecular ovarian cancer subtypes is critical to enable reliable preclinical testing. There are approximately 100 publicly available ovarian cancer cell lines but their cellular and molecular characteristics are largely undescribed. We have characterized 39 ovarian cancer cell lines under uniform conditions for growth characteristics, mRNA/microRNA expression, exon sequencing, drug response for clinically-relevant therapeutics and collated all available information on the original clinical features and site of origin. We tested for statistical associations between the cellular and molecular features of the lines and clinical features. Of the 39 ovarian cancer cell lines, 14 were assigned as high-grade serous, four serous-type, one low-grade serous and 20 non-serous type. Three morphological subtypes: Epithelial (n = 21), Round (n = 7) and Spindle (n = 12) were identified that showed distinct biological and molecular characteristics, including overexpression of cell movement and migration-associated genes in the Spindle subtype. Comparison with the original clinical data showed association of the spindle-like tumours with metastasis, advanced stage, suboptimal debulking and poor prognosis. In addition, the expression profiles of Spindle, Round and Epithelial morphologies clustered with the previously described C1-stromal, C5-mesenchymal and C4 ovarian subtype expression profiles respectively. Comprehensive profiling of 39 ovarian cancer cell lines under controlled, uniform conditions demonstrates clinically relevant cellular and genomic characteristics. This data provides a rational basis for selecting models to develop specific treatment approaches for histological and molecular subtypes of ovarian cancer.
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Corine M
authors.initials: CM
authors.lastname: Beaufort
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jean C A
authors.initials: JC
authors.lastname: Helmijr
authors.affiliation: Functional Genomics of Ovarian Cancer Laboratory, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
authors.forename: Anna M
authors.initials: AM
authors.lastname: Piskorz
authors.affiliation: Department of Medical Oncology and Center for Personalized Cancer Treatment, University Medical Center Utrecht, Utrecht The Netherlands.
authors.forename: Marlous
authors.initials: M
authors.lastname: Hoogstraat
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Kirsten
authors.initials: K
authors.lastname: Ruigrok-Ritstier
authors.affiliation: Department of Medical Oncology and Center for Personalized Cancer Treatment, University Medical Center Utrecht, Utrecht The Netherlands.
authors.forename: Nicolle
authors.initials: N
authors.lastname: Besselink
authors.affiliation: Molecular and Computational Diagnostics Laboratory, Cancer Research UK Cambridge Institute, University of Cambridge, Cambridge, United Kingdom.
authors.forename: Muhammed
authors.initials: M
authors.lastname: Murtaza
authors.affiliation: Center for Biomics, Erasmus MC, Rotterdam, The Netherlands.
authors.forename: Wilfred F J
authors.initials: WF
authors.lastname: van Ĳcken
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Anouk A J
authors.initials: AA
authors.lastname: Heine
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Marcel
authors.initials: M
authors.lastname: Smid
authors.affiliation: Department of Medical Oncology and Center for Personalized Cancer Treatment, University Medical Center Utrecht, Utrecht The Netherlands.
authors.forename: Marco J
authors.initials: MJ
authors.lastname: Koudijs
authors.affiliation: Functional Genomics of Ovarian Cancer Laboratory, Cancer Research UK Cambridge Institute, University of Cambridge, Li Ka Shing Centre, Cambridge, United Kingdom.
authors.forename: James D
authors.initials: JD
authors.lastname: Brenton
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Els M J J
authors.initials: EM
authors.lastname: Berns
authors.affiliation: Department of Medical Oncology, Erasmus MC Cancer Institute, Rotterdam, The Netherlands.
authors.forename: Jozien
authors.initials: J
authors.lastname: Helleman
mesh_terms: D000077216:Carcinoma, Ovarian Epithelial; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D035683:MicroRNAs / Q000235:genetics*; D009375:Neoplasms, Glandular and Epithelial / Q000378:metabolism / Q000473:pathology*; D010051:Ovarian Neoplasms / Q000378:metabolism / Q000473:pathology*
chemical_list: D035683:MicroRNAs