title: Novel high-grade serous epithelial ovarian cancer cell lines that reflect the molecular diversity of both the sporadic and hereditary disease.
abstract: Few cell line models of epithelial ovarian cancer (EOC) have been developed for the high-grade serous (HGS) subtype, which is the most common and lethal form of gynaecological cancer. Here we describe the establishment of six new EOC cell lines spontaneously derived from HGS tumors (TOV2978G, TOV3041G and TOV3291G) or ascites (OV866(2), OV4453 and OV4485). Exome sequencing revealed somatic TP53 mutations in five of the cell lines. One cell line has a novel BRCA1 splice-site mutation, and another, a recurrent BRCA2 nonsense mutation, both of germline origin. The novel BRCA1 mutation induced abnormal splicing, mRNA instability, resulting in the absence of BRCA1 protein. None of the cell lines harbor mutations in KRAS or BRAF, which are characteristic of other EOC subtypes. SNP arrays showed that all of the cell lines exhibited structural chromosomal abnormalities, copy number alterations and regions of loss of heterozygosity, consistent with those described for HGS. Four cell lines were able to produce 3D-spheroids, two exhibited anchorage-independent growth, and three (including the BRCA1 and BRCA2 mutated cell lines) formed tumors in SCID mice. These novel HGS EOC cell lines and their detailed characterization provide new research tools for investigating the most common and lethal form of EOC.
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Institut du cancer de Montréal, Montreal, Canada.
authors.forename: Hubert
authors.initials: H
authors.lastname: Fleury
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Institut du cancer de Montréal, Montreal, Canada.
authors.forename: Laudine
authors.initials: L
authors.lastname: Communal
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Institut du cancer de Montréal, Montreal, Canada.
authors.forename: Euridice
authors.initials: E
authors.lastname: Carmona
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Institut du cancer de Montréal, Montreal, Canada.
authors.forename: Lise
authors.initials: L
authors.lastname: Portelance
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, Canada.
authors.forename: Suzanna L
authors.initials: SL
authors.lastname: Arcand
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Department of Pathology, Centre hospitalier de l'Université de Montréal (CHUM), Montreal, Canada.
authors.forename: Kurosh
authors.initials: K
authors.lastname: Rahimi
authors.affiliation: The Research Institute of the McGill University Health Centre, Montreal, Canada.|Department of Human Genetics, McGill University, Montreal, Canada.|Department of Medicine, McGill University, Montreal, Canada.
authors.forename: Patricia N
authors.initials: PN
authors.lastname: Tonin
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Institut du cancer de Montréal, Montreal, Canada.|Division of Gynecologic Oncology, Université de Montréal, Montreal, Canada.|Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Diane
authors.initials: D
authors.lastname: Provencher
authors.affiliation: Centre de recherche du Centre hospitalier de l'Université de Montréal (CRCHUM), Montreal, Canada.|Institut du cancer de Montréal, Montreal, Canada.|Department of Medicine, Université de Montréal, Montreal, Canada.
authors.forename: Anne-Marie
authors.initials: AM
authors.lastname: Mes-Masson
keywords: BRCA mutations; cell lines; epithelial ovarian cancer; high-grade serous