The DOI matches its Crossref record; 13 of the 13 references it cites were found in a registry or an index.
An Epigenetic Signature in Peripheral Blood Predicts Active Ovarian Cancer
Open accessAbstract
BACKGROUND: Recent studies have shown that DNA methylation (DNAm) markers in peripheral blood may hold promise as diagnostic or early detection/risk markers for epithelial cancers. However, to date no study has evaluated the diagnostic and predictive potential of such markers in a large case control cohort and on a genome-wide basis. PRINCIPAL FINDINGS: By performing genome-wide DNAm profiling of a large ovarian cancer case control cohort, we here demonstrate that active ovarian cancer has a significant impact on the DNAm pattern in peripheral blood. Specifically, by measuring the methylation levels of over 27,000 CpGs in blood cells from 148 healthy individuals and 113 age-matched pre-treatment ovarian cancer cases, we derive a DNAm signature that can predict the presence of active ovarian cancer in blind test sets with an AUC of 0.8 (95% CI (0.74-0.87)). We further validate our findings in another independent set of 122 post-treatment cases (AUC = 0.76 (0.72-0.81)). In addition, we provide evidence for a significant number of candidate risk or early detection markers for ovarian cancer. Furthermore, by comparing the pattern of methylation with gene expression data from major blood cell types, we here demonstrate that age and cancer elicit common changes in the composition of peripheral blood, with a myeloid skewing that increases with age and which is further aggravated in the presence of ovarian cancer. Finally, we show that most cancer and age associated methylation variability is found at CpGs located outside of CpG islands. SIGNIFICANCE: Our results underscore the potential of DNAm profiling in peripheral blood as a tool for detection or risk-prediction of epithelial cancers, and warrants further in-depth and higher CpG coverage studies to further elucidate this role.
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Gene Ontology: tool for the unification of biology
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DAVID: Database for Annotation, Visualization, and Integrated Discovery
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Epigenetic differences arise during the lifetime of monozygotic twins
Fraga, M. F., Ballestar, E., Paz, M. F., Ropero, S., Setien, F., Ballestar, M. L., Heine-Suñer, D., Cigudosa, J. C., Urioste, M., Benitez, J., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0500398102 · Cited by 3,602
Capturing Heterogeneity in Gene Expression Studies by Surrogate Variable Analysis
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“lymphocyte ratio [25–29], a pattern consistent with our observation that granulocyte and T-lymphocyte specific genes were enriched”
BackgroundEpigenetic stem cell signature in cancer
Widschwendter, M., Fiegl, H., Egle, D., Mueller-Holzner, E., Spizzo, G., Marth, C., Weisenberger, D. J., Campan, M., Young, J., Jacobs, I., et al. (2007) · Nature Genetics · doi:10.1038/ng1941 · Cited by 1,143
Self-citationOhm, J. E., McGarvey, K. M., Yu, X., Cheng, L., Schuebel, K. E., Cope, L., Mohammad, H. P., Chen, W., Daniel, V. C., Yu, W., et al. (2007) · Nature Genetics · doi:10.1038/ng1972 · Cited by 1,130
Cited by
DNA methylation arrays as surrogate measures of cell mixture distribution
Houseman, E. A., Accomando, W. P., Koestler, D. C., Christensen, B. C., Marsit, C. J., Nelson, H. H., Wiencke, J. K., & Kelsey, K. T. (2012) · BMC Bioinformatics · doi:10.1186/1471-2105-13-86 · Cited by 3,175
Accounting for cellular heterogeneity is critical in epigenome-wide association studies
Jaffe, A. E., & Irizarry, R. A. (2014) · Genome Biology · doi:10.1186/gb-2014-15-2-r31 · Cited by 1,067
Sensitive tumour detection and classification using plasma cell-free DNA methylomes
Shen, S. Y., Singhania, R., Fehringer, G., Chakravarthy, A., Roehrl, M. H. A., Chadwick, D., Zuzarte, P. C., Borgida, A., Wang, T. T., Li, T., et al. (2018) · Nature · doi:10.1038/s41586-018-0703-0 · Cited by 983
Age-dependent DNA methylation of genes that are suppressed in stem cells is a hallmark of cancer
Teschendorff, A. E., Menon, U., Gentry-Maharaj, A., Ramus, S. J., Weisenberger, D. J., Shen, H., Campan, M., Noushmehr, H., Bell, C. G., Maxwell, A. P., et al. (2010) · Genome Research · doi:10.1101/gr.103606.109 · Cited by 855
Self-citationTobacco-smoking-related differential DNA methylation: 27K discovery and replication
Breitling, L. P., Yang, R., Korn, B., Burwinkel, B., & Brenner, H. (2011) · The American Journal of Human Genetics · doi:10.1016/j.ajhg.2011.03.003 · Cited by 640
Metadata
- Authors
- Teschendorff, A. E., Menon, U., Gentry-Maharaj, A., Ramus, S. J., Gayther, S. A., Apostolidou, S., Jones, A., Lechner, M., Beck, S., Jacobs, I. J., & Widschwendter, M.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2009-12-18
- Volume
- 4
- Issue
- 12
- Pages
- e8274
- ISSN
- 1932-6203 (ISSN-L)
- OpenAlex
- W2095682261
- Cited by
- 359
- References
- 13
- FWCI
- 6.72
- Type
- journal article
- Language
- en
- Open access
- gold
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- Teschendorff, A. E., Menon, U., Gentry-Maharaj, A., Ramus, S. J., Gayther, S. A., Apostolidou, S., Jones, A., Lechner, M., Beck, S., Jacobs, I. J., & Widschwendter, M. (2009). An Epigenetic Signature in Peripheral Blood Predicts Active Ovarian Cancer. PLoS ONE. https://doi.org/10.1371/journal.pone.0008274
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