@article{0e2d6388d5994cfd8b2763b92e80b469,
title = "Integrated Genomic, Epigenomic, and Expression Analyses of Ovarian Cancer Cell Lines",
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. The overall survival of patients with late-stage ovarian cancer is dismal. To identify therapeutic opportunities, Papp et al. integrate genomic, epigenomic, and expression analyses to provide a resource of molecular abnormalities in ovarian cancer cell lines and use these to identify tumors sensitive to PARP, MEK, and PI3K inhibitors.",
keywords = "cancer cell lines, cancer genomics, drug response, gene fusions, ovarian cancer, structural variants",
author = "Eniko Papp and Dorothy Hallberg and Konecny, {Gottfried E.} and Bruhm, {Daniel C.} and Vilmos Adleff and Micha{\"e}l No{\"e} and Ioannis Kagiampakis and Doreen Palsgrove and Dylan Conklin and Yasuto Kinose and White, {James R.} and Press, {Michael F.} and Ronny Drapkin and Hariharan Easwaran and Baylin, {Stephen B.} and Dennis Slamon and Velculescu, {Victor E.} and Scharpf, {Robert B.}",
note = "Funding Information: We would like to thank Carolyn Hruban for help with artwork and members of our laboratories for critical review of this manuscript. This work was supported in part by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation ; the Commonwealth Foundation ; The Cigarette Restitution Fund ; NIH grants CA121113 , CA006973 , and CA180950 ; and Department of Defense CDMRP Team Innovator Award W81XWH-14-1-0385 . Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research . Funding Information: We would like to thank Carolyn Hruban for help with artwork and members of our laboratories for critical review of this manuscript. This work was supported in part by the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation; the Commonwealth Foundation; The Cigarette Restitution Fund; NIH grants CA121113, CA006973, and CA180950; and Department of Defense CDMRP Team Innovator Award W81XWH-14-1-0385. Stand Up To Cancer is a program of the Entertainment Industry Foundation administered by the American Association for Cancer Research. Funding Information: V.E.V. is a founder of the Personal Genome Diagnostics, is a member of its Scientific Advisory Board and Board of Directors, and owns a Personal Genome Diagnostics stock, which is subject to certain restrictions under university policy. V.E.V. is also on the Scientific Advisory Board for Ignyta. Under separate licensing agreements between Agios Pharmaceuticals, Exact Sciences Corporation, Myriad Genetics, Personal Genome Diagnostics, Qiagen, Sysmex-Inostics, and the Johns Hopkins University, V.E.V. is entitled to a share of royalty and milestone payments received by the University on sales of products related to research described in this manuscript. The terms of this arrangement are being managed by the Johns Hopkins University in accordance with its conflict of interest policies. D.S. has a leadership role with Biomarin, is a consultant for and has recieved research funding from Novartis, owns stock of and has recieved research funding from Pfizer, and is a consultant for Eli Lilly. Publisher Copyright: {\textcopyright} 2018 The Authors",
year = "2018",
month = nov,
day = "27",
doi = "10.1016/j.celrep.2018.10.096",
language = "English (US)",
volume = "25",
pages = "2617--2633",
journal = "Cell Reports",
issn = "2211-1247",
publisher = "Cell Press",
number = "9",
}