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PMID: 16036111 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

High-resolution mapping of genomic imbalance and identification of gene expression profiles associated with differential chemotherapy response in serous epithelial ovarian cancer.

Neoplasia (New York, N.Y.) ·Vol. 7 ·No. 6 ·2005-06-00 ·Pages 603-13

Bernardini M, Lee CH, Beheshti B, Prasad M, Albert M, Marrano P, Begley H, Shaw P, Covens A, Murphy J, Rosen B, Minkin S, Squire JA, Macgregor PF

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.

MeSH Terms
Cell Nucleus/metabolism Chromosome Mapping/methods DNA/chemistry Drug Resistance, Neoplasm Epithelial Cells/cytology Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Genome Humans In Situ Hybridization, Fluorescence Nucleic Acid Hybridization Oligonucleotide Array Sequence Analysis Ovarian Neoplasms/genetics,metabolism,pathology RNA/chemistry
Chemicals
RNA DNA
Authors & Affiliations
14 authors, click to expand affiliations / ORCID
Bernardini Marcus
Ontario Cancer Institute, Princess Margaret Hospital, University Health Network, Toronto, Ontario, Canada.
Lee Chung-Hae
Beheshti Ben
Prasad Mona
Albert Monique
Marrano Paula
Begley Heather
Shaw Patricia
Covens Al
Murphy Joan
Rosen Barry
Minkin Salomon
Squire Jeremy A
Macgregor Pascale F
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Article Info
Journal
Neoplasia (New York, N.Y.)
Abbr.
Neoplasia
ISSN
1522-8002
DOI
10.1593/neo.04760
Published
2005-06-00
Pages
603-13
Language
English
Region
United States
NLM ID
100886622
PMCID
PMC1501280
Subset
IM
External Links
PubMed source DOI: 10.1593/neo.04760 PMC Full Text
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