Please use this identifier to cite or link to this item: https://doi.org/10.1371/journal.pone.0028141
Title: Genome-scale screen for DNA methylation-based detection markers for ovarian cancer
Authors: Campan M.
Moffitt M.
Houshdaran S.
Shen H. 
Widschwendter M.
Daxenbichler G.
Long T.
Marth C.
Laird-Offringa I.A.
Press M.F.
Dubeau L.
Siegmund K.D.
Wu A.H.
Groshen S.
Chandavarkar U.
Roman L.D.
Berchuck A.
Pearce C.L.
Laird P.W.
Keywords: CA 125 antigen
DNA
tumor marker
CA 125 antigen
DNA
tumor marker
article
cancer diagnosis
cancer patient
cancer recurrence
cancer surgery
clear cell carcinoma
controlled study
CpG island
DNA determination
DNA extraction
DNA methylation
endometrioid carcinoma
female
genetic screening
human
leukocyte
mucinous carcinoma
ovary cancer
promoter region
sensitivity analysis
biosynthesis
blood
blood clotting
gene expression regulation
genetic epigenesis
genetics
genotype
human genome
kinetics
longitudinal study
metabolism
ovary tumor
reproducibility
risk
Blood Coagulation
CA-125 Antigen
CpG Islands
DNA
DNA Methylation
Epigenesis, Genetic
Female
Gene Expression Regulation, Neoplastic
Genome, Human
Genotype
Humans
Kinetics
Longitudinal Studies
Odds Ratio
Ovarian Neoplasms
Reproducibility of Results
Tumor Markers, Biological
Issue Date: 2011
Citation: Campan M., Moffitt M., Houshdaran S., Shen H., Widschwendter M., Daxenbichler G., Long T., Marth C., Laird-Offringa I.A., Press M.F., Dubeau L., Siegmund K.D., Wu A.H., Groshen S., Chandavarkar U., Roman L.D., Berchuck A., Pearce C.L., Laird P.W. (2011). Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS ONE 6 (12) : e28141. ScholarBank@NUS Repository. https://doi.org/10.1371/journal.pone.0028141
Abstract: Background: The identification of sensitive biomarkers for the detection of ovarian cancer is of high clinical relevance for early detection and/or monitoring of disease recurrence. We developed a systematic multi-step biomarker discovery and verification strategy to identify candidate DNA methylation markers for the blood-based detection of ovarian cancer. Methodology/Principal Findings: We used the Illumina Infinium platform to analyze the DNA methylation status of 27,578 CpG sites in 41 ovarian tumors. We employed a marker selection strategy that emphasized sensitivity by requiring consistency of methylation across tumors, while achieving specificity by excluding markers with methylation in control leukocyte or serum DNA. Our verification strategy involved testing the ability of identified markers to monitor disease burden in serially collected serum samples from ovarian cancer patients who had undergone surgical tumor resection compared to CA-125 levels. We identified one marker, IFFO1 promoter methylation (IFFO1-M), that is frequently methylated in ovarian tumors and that is rarely detected in the blood of normal controls. When tested in 127 serially collected sera from ovarian cancer patients, IFFO1-M showed post-resection kinetics significantly correlated with serum CA-125 measurements in six out of 16 patients. Conclusions/Significance: We implemented an effective marker screening and verification strategy, leading to the identification of IFFO1-M as a blood-based candidate marker for sensitive detection of ovarian cancer. Serum levels of IFFO1-M displayed post-resection kinetics consistent with a reflection of disease burden. We anticipate that IFFO1-M and other candidate markers emerging from this marker development pipeline may provide disease detection capabilities that complement existing biomarkers. © 2011 Campan et al.
Source Title: PLoS ONE
URI: https://scholarbank.nus.edu.sg/handle/10635/162019
ISSN: 19326203
DOI: 10.1371/journal.pone.0028141
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