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Ovarian Cancer pp 35–51Cite as

Integrative Prediction of Gene Function and Platinum-Free Survival from Genomic and Epigenetic Features in Ovarian Cancer

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Part of the book series: Methods in Molecular Biology ((MIMB,volume 1049))

Abstract

The identification of genetic and epigenetic alterations from primary tumor cells has become a common method to discover genes critical to the development, progression, and therapeutic resistance of cancer. We seek to identify those genetic and epigenetic aberrations that have the most impact on gene function within the tumor. First, we perform a bioinformatics analysis of copy number variation (CNV) and DNA methylation covering the genetic landscape of ovarian cancer tumor cells. We were specifically interested in copy number variation as our base genomic property in the prediction of tumor suppressors and oncogenes in the altered ovarian tumor. We identify changes in DNA methylation and expression specifically for all amplified and deleted genes. We statistically define tumor suppressor and oncogenic gene function from integrative analysis of three modalities: copy number variation, DNA methylation, and gene expression. Our method (1) calculates the extent of genomic and epigenetic alterations of defined tumor suppressor and oncogenic features for the functional prediction of significant ovarian cancer gene candidates and (2) identifies the functional activity or inactivity of known tumor suppressors and oncogenes in ovarian cancer. We applied our protocol on 42 primary serous ovarian cancer samples using MOMA-ROMA representational array assays. Additionally, we provide the basis for incorporating epigenetic profiles of ovarian tumors for the purposes of platinum-free survival prediction in the context of TCGA data.

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Author information

Authors and Affiliations

  1. Bioinformatics and Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA

    Kazimierz O. Wrzeszczynski

  2. Philips Research North America, Briarcliff Manor, NY, USA

    Vinay Varadan, Sitharthan Kamalakaran & Nevenka Dimitrova

  3. Department of Surgery, Gynecology Service, Memorial Sloan-Kettering Cancer Center, New York, NY, USA

    Douglas A. Levine

  4. Hofstra North Shore-LIJ School of Medicine, Hofstra University, Hempstead, NY, USA

    Robert Lucito

Authors
  1. Kazimierz O. Wrzeszczynski
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  2. Vinay Varadan
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  3. Sitharthan Kamalakaran
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  4. Douglas A. Levine
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  5. Nevenka Dimitrova
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  6. Robert Lucito
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Editor information

Editors and Affiliations

  1. Group of Experimental Therapeutics, Federal State Institution N.N.Petrov Res Institute of Oncology, St. Petersburg, Russia

    Anastasia Malek

  2. Labs of Molecular Tumor Pathology & Func, Charité - Universitatsmedizin Berlin, Berlin, Germany

    Oleg Tchernitsa

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Wrzeszczynski, K.O., Varadan, V., Kamalakaran, S., Levine, D.A., Dimitrova, N., Lucito, R. (2013). Integrative Prediction of Gene Function and Platinum-Free Survival from Genomic and Epigenetic Features in Ovarian Cancer. In: Malek, A., Tchernitsa, O. (eds) Ovarian Cancer. Methods in Molecular Biology, vol 1049. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-62703-547-7_4

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  • DOI: https://doi.org/10.1007/978-1-62703-547-7_4

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  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-62703-546-0

  • Online ISBN: 978-1-62703-547-7

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