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

Eniko Papp, Dorothy Hallberg, Gottfried E. Konecny, Daniel C. Bruhm, Vilmos Adleff, Michaël Noë, Ioannis Kagiampakis, Doreen Palsgrove, Dylan Conklin, Yasuto Kinose, James R. White, Michael F. Press, Ronny Drapkin, Hariharan Easwaran, Stephen B. Baylin, Dennis Slamon, Victor E. Velculescu, Robert B. Scharpf

Research output: Contribution to journalArticle

9 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)2617-2633
Number of pages17
JournalCell Reports
Volume25
Issue number9
DOIs
StatePublished - Nov 27 2018
Externally publishedYes

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Keywords

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

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Papp, E., Hallberg, D., Konecny, G. E., Bruhm, D. C., Adleff, V., Noë, M., Kagiampakis, I., Palsgrove, D., Conklin, D., Kinose, Y., White, J. R., Press, M. F., Drapkin, R., Easwaran, H., Baylin, S. B., Slamon, D., Velculescu, V. E., & Scharpf, R. B. (2018). Integrated Genomic, Epigenomic, and Expression Analyses of Ovarian Cancer Cell Lines. Cell Reports, 25(9), 2617-2633. https://doi.org/10.1016/j.celrep.2018.10.096