title: High-resolution mapping of genomic imbalance and identification of gene expression profiles associated with differential chemotherapy response in serous epithelial ovarian cancer.
abstract: Array comparative genomic hybridization (aCGH) and microarray expression profiling were used to subclassify DNA and RNA alterations associated with differential response to chemotherapy in ovarian cancer. Two to 4 Mb interval arrays were used to map genomic imbalances in 26 sporadic serous ovarian tumors. Cytobands 1p36, 1q42-44, 6p22.1-p21.2, 7q32.1-q34 9q33.3-q34.3, 11p15.2, 13q12.2-q13.1, 13q21.31, 17q11.2, 17q24.2-q25.3, 18q12.2, and 21q21.2-q21.3 were found to be statistically associated with chemotherapy response, and novel regions of loss at 15q11.2-q15.1 and 17q21.32-q21.33 were identified. Gene expression profiles were obtained from a subset of these tumors and identified a group of genes whose differential expression was significantly associated with drug resistance. Within this group, five genes (GAPD, HMGB2, HSC70, GRP58, and HMGB1), previously shown to form a nuclear complex associated with resistance to DNA conformation-altering chemotherapeutic drugs in in vitro systems, may represent a novel class of genes associated with in vivo drug response in ovarian cancer patients. Although RNA expression change indicated only weak DNA copy number dependence, these data illustrate the value of molecular profiling at both the RNA and DNA levels to identify small genomic regions and gene subsets that could be associated with differential chemotherapy response in ovarian cancer.
authors.affiliation: Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
authors.forename: Marcus
authors.initials: M
authors.lastname: Bernardini
authors.forename: Chung-Hae
authors.initials: CH
authors.lastname: Lee
authors.forename: Ben
authors.initials: B
authors.lastname: Beheshti
authors.forename: Mona
authors.initials: M
authors.lastname: Prasad
authors.forename: Monique
authors.initials: M
authors.lastname: Albert
authors.forename: Paula
authors.initials: P
authors.lastname: Marrano
authors.forename: Heather
authors.initials: H
authors.lastname: Begley
authors.forename: Patricia
authors.initials: P
authors.lastname: Shaw
authors.forename: Al
authors.initials: A
authors.lastname: Covens
authors.forename: Joan
authors.initials: J
authors.lastname: Murphy
authors.forename: Barry
authors.initials: B
authors.lastname: Rosen
authors.forename: Salomon
authors.initials: S
authors.lastname: Minkin
authors.forename: Jeremy A
authors.initials: JA
authors.lastname: Squire
authors.forename: Pascale F
authors.initials: PF
authors.lastname: Macgregor
mesh_terms: D002467:Cell Nucleus / Q000378:metabolism; D002874:Chromosome Mapping / Q000379:methods*; D004247:DNA / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D004847:Epithelial Cells / Q000166:cytology; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D016678:Genome; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D009693:Nucleic Acid Hybridization; D020411:Oligonucleotide Array Sequence Analysis; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D012313:RNA / Q000737:chemistry
chemical_list: D012313:RNA; D004247:DNA