title: Integrative prediction of gene function and platinum-free survival from genomic and epigenetic features in ovarian cancer.
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.
authors.affiliation: Bioinformatics and Genomics, Cold Spring Harbor Laboratory, Cold Spring Harbor, NY, USA.
authors.forename: Kazimierz O
authors.initials: KO
authors.lastname: Wrzeszczynski
authors.forename: Vinay
authors.initials: V
authors.lastname: Varadan
authors.forename: Sitharthan
authors.initials: S
authors.lastname: Kamalakaran
authors.forename: Douglas A
authors.initials: DA
authors.lastname: Levine
authors.forename: Nevenka
authors.initials: N
authors.lastname: Dimitrova
authors.forename: Robert
authors.initials: R
authors.lastname: Lucito
mesh_terms: D045744:Cell Line, Tumor; D056915:DNA Copy Number Variations / Q000235:genetics*; D019175:DNA Methylation / Q000235:genetics; D044127:Epigenesis, Genetic; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D015894:Genome, Human; D006801:Humans; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D010984:Platinum / Q000627:therapeutic use; D016019:Survival Analysis
chemical_list: D010984:Platinum