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Cell Rep. 2018 Nov 27;25(9):2617-2633. doi: 10.1016/j.celrep.2018.10.096.

Integrated Genomic, Epigenomic, and Expression Analyses of Ovarian Cancer Cell Lines.

Author information

1
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
2
Division of Hematology and Oncology, Jonsson Comprehensive Cancer Center, David Geffen School of Medicine at UCLA, Los Angeles, CA 90024, USA.
3
Department of Obstetrics and Gynecology Penn Ovarian Cancer Research Center, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
4
Department of Pathology, Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, CA 90033, USA.
5
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: velculescu@jhmi.edu.
6
The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA. Electronic address: rscharpf@jhu.edu.

Abstract

To improve our understanding of ovarian cancer, we performed genome-wide analyses of 45 ovarian cancer cell lines. Given the challenges of genomic analyses of tumors without matched normal samples, we developed approaches for detection of somatic sequence and structural changes and integrated these with epigenetic and expression alterations. Alterations not previously implicated in ovarian cancer included amplification or overexpression of ASXL1 and H3F3B, deletion or underexpression of CDC73 and TGF-beta receptor pathway members, and rearrangements of YAP1-MAML2 and IKZF2-ERBB4. Dose-response analyses to targeted therapies revealed unique molecular dependencies, including increased sensitivity of tumors with PIK3CA and PPP2R1A alterations to PI3K inhibitor GNE-493, MYC amplifications to PARP inhibitor BMN673, and SMAD3/4 alterations to MEK inhibitor MEK162. Genome-wide rearrangements provided an improved measure of sensitivity to PARP inhibition. This study provides a comprehensive and broadly accessible resource of molecular information for the development of therapeutic avenues in ovarian cancer.

KEYWORDS:

cancer cell lines; cancer genomics; drug response; gene fusions; ovarian cancer; structural variants

PMID:
30485824
DOI:
10.1016/j.celrep.2018.10.096
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