Integrative prediction of gene function and platinum-free survival from genomic and epigenetic features in ovarian cancer

Wrzeszczynski, K. O., Varadan, V., Kamalakaran, S., Levine, D. A., Dimitrova, N., Lucito, R. (August 2013) Integrative prediction of gene function and platinum-free survival from genomic and epigenetic features in ovarian cancer. Methods Mol Biol, 1049. pp. 35-51. ISSN 1940-6029 (Electronic)1064-3745 (Linking)

URL: http://www.ncbi.nlm.nih.gov/pubmed/23913207
DOI: 10.1007/978-1-62703-547-7_4

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.

Item Type: Paper
Subjects: diseases & disorders > cancer
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification
bioinformatics > genomics and proteomics > genetics & nucleic acid processing
bioinformatics > genomics and proteomics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > epigenetics
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > epigenetics

bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > genes, structure and function
diseases & disorders > cancer > cancer types > ovarian cancer
CSHL Authors:
Communities: CSHL labs > Lucito lab
Depositing User: Matt Covey
Date: August 2013
Date Deposited: 17 Sep 2013 19:46
Last Modified: 17 Sep 2013 19:46
Related URLs:
URI: http://repository.cshl.edu/id/eprint/28612

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