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.
Highlights
Epithelial ovarian cancer is the most lethal gynaecological malignancy in the Western world and advanced disease remains incurable for the majority of patients
COLO720E has been described to be mixture of the COLO684 and COLO685 cell lines which are both derived from uterine adenocarcinoma [30]
Defective MMR is associated with a large variability in the length of these repeats which is called micro-satellite instability (MSI)
Summary
Epithelial ovarian cancer is the most lethal gynaecological malignancy in the Western world and advanced disease remains incurable for the majority of patients. High-grade serous (HGS) carcinoma represents 80% of ovarian cancers and is defined by TP53 mutation (96%), homologous recombination DNA repair defects (,50%), CCNE1 amplification and genomic instability [4,5,6]. Low-grade serous carcinomas are TP53 wildtype and show frequently activating RAS pathway mutations [7,8]. The remaining histiotypes are mucinous, endometrioid and clear cell [3]. Activating RAS pathway mutations are found in ,40% of the mucinous tumours while endometrioid and clear cell tumours have PIK3CA (PI3Kinase component, 12%, 31% respectively), and ARID1A mutations (30%, 46%, respectively) [4,5,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
