Distinctive DNA methylation patterns of cell-free plasma DNA in women with malignant ovarian tumors.
OBJECTIVE
Epithelial ovarian carcinoma (OvCa) is rarely detected early, and it is also difficult to determine whether an adnexal mass is benign or malignant. Previously, we noted differences in methylation patterns of cell-free plasma DNA (cfpDNA) in women without disease compared to patients with OvCa. In this work, we investigated whether methylation patterns of cfpDNA can differentiate between benign and malignant tumors.


METHODS
Methylation patterns in cfpDNA were determined in three cohorts (30 samples each) using a microarray-based assay (MethDet 56). Principal component analysis, supervised clustering, linear discrimination analysis, and 25 rounds of 5-fold cross-validation were used to determine informative genes and assess the sensitivity and specificity of differentiating between OvCa vs. healthy control (HC), benign ovarian disease (mostly serous cystadenoma, BOD) vs. HC, and OvCa vs. BOD samples.


RESULTS
Differential methylation of three promoters (RASSF1A, CALCA, and EP300) differentiated between OvCa vs. HC with a sensitivity of 90.0% and a specificity of 86.7%. Three different promoters (BRCA1, CALCA, and CDKN1C) were informative for differentiating between BOD vs. HC, with a sensitivity of 90.0% and a specificity of 76.7%. Finally, two promoters (RASSF1A and PGR-PROX) were informative for differentiating between OvCa vs. BOD, with a sensitivity of 80.0% and a specificity of 73.3%.


CONCLUSIONS
This proof-of-principle data show that differential methylation of promoters in cfpDNA may be a useful biomarker to differentiate between certain benign and malignant ovarian tumors.
Rush University Medical Center, Department of Neurological Sciences, Multiple Sclerosis Center, 1745 W. Harrison Street, Ste. 309, Chicago, IL 60612, USA.
Thomas E
TE
Liggett
Anatoliy
A
Melnikov
Qilong
Q
Yi
Charles
C
Replogle
Wei
W
Hu
Jacob
J
Rotmensch
Aparna
A
Kamat
Anil K
AK
Sood
Victor
V
Levenson
D000368:Aged; D000369:Aged, 80 and over; D019175:DNA Methylation; D004273:DNA, Neoplasm / Q000097:blood* / Q000235:genetics; D003937:Diagnosis, Differential; D005260:Female; D006801:Humans; D008875:Middle Aged; D010049:Ovarian Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics; D010051:Ovarian Neoplasms / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
D004273:DNA, Neoplasm