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Int. J. Mol. Sci. 2015, 16(12), 29654-29662; doi:10.3390/ijms161226180

Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer

1
Department of Basic Oncology, Oncology Institute, Istanbul University, Istanbul 34093, Turkey
2
Department of General Surgery, Istanbul Medical Faculty, Istanbul University, Istanbul 34093, Turkey
3
Institute of Clinical Chemistry and Clinical Pharmacology, University of Bonn, Bonn D-53127, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: William Chi-shing Cho
Received: 2 September 2015 / Revised: 9 November 2015 / Accepted: 24 November 2015 / Published: 11 December 2015
(This article belongs to the Collection Advances in Molecular Oncology)
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Abstract

Circulating nucleic acids (CNAs) are under investigation as a liquid biopsy in cancer as potential non-invasive biomarkers, as stable structure in circulation nucleosomes could be valuable sources for detection of cancer-specific alterations in histone modifications. Our interest is in histone methylation marks with a focus on colorectal cancer, one of the leading cancers respective the incidence and mortality. Our previous work included the analysis of trimethylations of lysine 9 on histone 3 (H3K9me3) and of lysine 20 on histone 4 (H4K20me3) by chromatin immuno- precipitation-related PCR in circulating nucleosomes. Here we asked whether global immunologic measurement of histone marks in circulation could be a suitable approach to show their potential as biomarkers. In addition to H3K9me3 and H4K20me3 we also measured H3K27me3 in plasma samples from CRC patients (n = 63) and cancer free individuals (n = 40) by ELISA-based methylation assays. Our results show that of three marks, the amounts of H3K27me3 (p = 0.04) and H4K20me3 (p < 0.001) were significantly lower in CRC patients than in healthy controls. For H3K9me3 similar amounts were measured in both groups. Areas under the curve (AUC) in receiver operating characteristic (ROC) curves indicating the power of CRC detection were 0.620 for H3K27me3, 0.715 for H4K20me3 and 0.769 for the combination of both markers. In conclusion, findings of this preliminary study reveal the potential of blood-based detection of CRC by quantification of histone methylation marks and the additive effect of the marker combination. View Full-Text
Keywords: nucleosomes; histone modification; immunoassay; colorectal cancer nucleosomes; histone modification; immunoassay; colorectal cancer
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. (CC BY 4.0).

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Gezer, U.; Yörüker, E.E.; Keskin, M.; Kulle, C.B.; Dharuman, Y.; Holdenrieder, S. Histone Methylation Marks on Circulating Nucleosomes as Novel Blood-Based Biomarker in Colorectal Cancer. Int. J. Mol. Sci. 2015, 16, 29654-29662.

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