Skip to main content

Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.

Publication ,  Journal Article
Campan, M; Moffitt, M; Houshdaran, S; Shen, H; Widschwendter, M; Daxenbichler, G; Long, T; Marth, C; Laird-Offringa, IA; Press, MF; Dubeau, L ...
Published in: PLoS One
2011

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.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

12

Start / End Page

e28141

Location

United States

Related Subject Headings

  • Reproducibility of Results
  • Ovarian Neoplasms
  • Odds Ratio
  • Longitudinal Studies
  • Kinetics
  • Humans
  • Genotype
  • Genome, Human
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Campan, M., Moffitt, M., Houshdaran, S., Shen, H., Widschwendter, M., Daxenbichler, G., … Laird, P. W. (2011). Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS One, 6(12), e28141. https://doi.org/10.1371/journal.pone.0028141
Campan, Mihaela, Melissa Moffitt, Sahar Houshdaran, Hui Shen, Martin Widschwendter, Günter Daxenbichler, Tiffany Long, et al. “Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.PLoS One 6, no. 12 (2011): e28141. https://doi.org/10.1371/journal.pone.0028141.
Campan M, Moffitt M, Houshdaran S, Shen H, Widschwendter M, Daxenbichler G, et al. Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS One. 2011;6(12):e28141.
Campan, Mihaela, et al. “Genome-scale screen for DNA methylation-based detection markers for ovarian cancer.PLoS One, vol. 6, no. 12, 2011, p. e28141. Pubmed, doi:10.1371/journal.pone.0028141.
Campan M, Moffitt M, Houshdaran S, Shen H, Widschwendter M, Daxenbichler G, Long T, Marth C, Laird-Offringa IA, Press MF, Dubeau L, Siegmund KD, Wu AH, Groshen S, Chandavarkar U, Roman LD, Berchuck A, Pearce CL, Laird PW. Genome-scale screen for DNA methylation-based detection markers for ovarian cancer. PLoS One. 2011;6(12):e28141.

Published In

PLoS One

DOI

EISSN

1932-6203

Publication Date

2011

Volume

6

Issue

12

Start / End Page

e28141

Location

United States

Related Subject Headings

  • Reproducibility of Results
  • Ovarian Neoplasms
  • Odds Ratio
  • Longitudinal Studies
  • Kinetics
  • Humans
  • Genotype
  • Genome, Human
  • General Science & Technology
  • Gene Expression Regulation, Neoplastic