Identification of candidate methylation-responsive genes in ovarian cancer.
BACKGROUND
Aberrant methylation of gene promoter regions has been linked to changes in gene expression in cancer development and progression. Genes associated with CpG islands (CGIs) are especially prone to methylation, but not all CGI-associated genes display changes in methylation patterns in cancers.


RESULTS
In order to identify genes subject to regulation by methylation, we conducted gene expression profile analyses of an ovarian cancer cell line (OVCAR-3) before and after treatment with the demethylating agent 5-aza-deoxycytidine (5-aza-dC). An overlapping subset of these genes was found to display significant differences in gene expression between normal ovarian surface epithelial cells and malignant cells isolated from ovarian carcinomas. While 40% of all human genes are associated with CGIs, > 94% of the overlapping subset of genes is associated with CGIs. The predicted change in methylation status of genes randomly selected from the overlapping subset was experimentally verified.


CONCLUSIONS
We conclude that correlating genes that are upregulated in response to 5-aza-dC treatment of cancer cell lines with genes that are down-regulated in cancer cells may be a useful method to identify genes experiencing epigenetic-mediated changes in expression over cancer development.
Menendez
Laura
L
Department of Genetics, University of Georgia, Athens, GA 30605, USA. lmenen@uga.edu
Walker
DeEtte
D
Matyunina
Lilya V
LV
Dickerson
Erin B
EB
Bowen
Nathan J
NJ
Polavarapu
Nalini
N
Benigno
Benedict B
BB
McDonald
John F
JF
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D001374:Azacitidine / Q000031:analogs & derivatives / Q000494:pharmacology; D045744:Cell Line, Tumor; D018899:CpG Islands / Q000187:drug effects; D019175:DNA Methylation / Q000187:drug effects; D000077209:Decitabine; D044127:Epigenesis, Genetic; D005260:Female; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D006801:Humans; D010051:Ovarian Neoplasms / Q000235:genetics* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D000077209:Decitabine; D001374:Azacitidine