Methylation microarray analysis of late-stage ovarian carcinomas distinguishes progression-free survival in patients and identifies candidate epigenetic markers.
OBJECTIVE
The purpose of this study was to profile methylation alterations of CpG islands in ovarian tumors and to identify candidate markers for diagnosis and prognosis of the disease.


METHODS
A global analysis of DNA methylation using a novel microarray approach called differential methylation hybridization was performed on 19 patients with stage III and IV ovarian carcinomas.


RESULTS
Hierarchical clustering identified two groups of patients with distinct methylation profiles. Tumors from group 1 contained high levels of concurrent methylation, whereas group 2 tumors had lower tumor methylation levels. The duration of progression-free survival after chemotherapy was significantly shorter for patients in group 1 compared with group 2 (P < 0.001). Differential methylation in tumors was independently confirmed by methylation-specific PCR.


CONCLUSIONS
The data suggest that a higher degree of CpG island methylation is associated with early disease recurrence after chemotherapy. The differential methylation hybridization assay also identified a select group of CpG island loci that are potentially useful as epigenetic markers for predicting treatment outcome in ovarian cancer patients.
Department of Pathology and Anatomical Sciences, Ellis Fischel Cancer Center, University of Missouri, Columbia, Missouri 65203, USA.
Susan H
SH
Wei
Chuan-Mu
CM
Chen
Gordon
G
Strathdee
Jaturon
J
Harnsomburana
Chi-Ren
CR
Shyu
Farahnaz
F
Rahmatpanah
Huidong
H
Shi
Shu-Wing
SW
Ng
Pearlly S
PS
Yan
Kenneth P
KP
Nephew
Robert
R
Brown
Tim Hui-Ming
TH
Huang
D014408:Biomarkers, Tumor / Q000032:analysis*; D002291:Carcinoma, Papillary / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D018899:CpG Islands / Q000235:genetics*; D018284:Cystadenocarcinoma, Serous / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism; D019175:DNA Methylation; D017931:DNA Primers / Q000737:chemistry; D004273:DNA, Neoplasm / Q000032:analysis; D018572:Disease-Free Survival; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D009367:Neoplasm Staging; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D010051:Ovarian Neoplasms / Q000175:diagnosis / Q000235:genetics* / Q000378:metabolism
D014408:Biomarkers, Tumor; D017931:DNA Primers; D004273:DNA, Neoplasm