Elsevier

Neoplasia

Volume 7, Issue 6, June 2005, Pages 603-613, IN17-IN20
Neoplasia

High-Resolution Mapping of Genomic Imbalance and Identification of Gene Expression Profiles Associated with Differential Chemotherapy Response in Serous Epithelial Ovarian Cancer1,*

https://doi.org/10.1593/neo.04760Get rights and content
Under a Creative Commons license
open access

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, iq42-44, 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 15g11.2q15.1 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.

Keywords

cisplatin
taxol
gene amplification
gene deletion
microarray data mining

Abbreviations

aCGH
array comparative genomic hybridization
FFPE
formalin-fixed paraffinembedded
GAPD
glyceraldehyde phosphate dehydrogenase
GRP58
glucose-regulatory protein 58
HMGB1
high-mobility group beta 1
HMGB2
high-mobility group beta 2
HSC70
heat shock cognate protein 70
PAM
prediction analysis of microarrays
SAM
significance analysis of microarrays
SEOC
serous epithelial ovarian cancer

Cited by (0)

1

This study was supported by a grant award from the Ontario Cancer Research Network (funded through the Government of Ontario), Genome Canada, and the Ovarian Fashion Show Committee (Princess Margaret Hospital). M.B. was supported by the Kristi Pia Memorial Fellowship. The Toronto Ovarian Tissue Bank and Database was funded, in part, by the National Ovarian Cancer Association and the St. George's Society.

*

This article refers to supplementary material, which is designated by “W” (ie, Table W1, Figure W1) and is available online at www.bcdecker.com

2

Present address: Canadian Breast Cancer Foundation - Ontario Chapter, 790 Bay Street, Suite 1000, Toronto, Ontario, M5G 1N8, Canada.