Correlation of histone methyl marks with circulating nucleosomes in blood plasma of cancer patients

Gezer,Ugur; Mert,Ufuk; Özgür,Emre; Yörüker,Ebru  E.; Holdenrieder,Stefan; Dalay,Nejat

doi:10.3892/ol.2012.600

May 2012 Volume 3 Issue 5

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May 2012 Volume 3 Issue 5

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Article

Correlation of histone methyl marks with circulating nucleosomes in blood plasma of cancer patients

Authors:
- Ugur Gezer
- Ufuk Mert
- Emre Özgür
- Ebru E. Yörüker
- Stefan Holdenrieder
- Nejat Dalay
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Affiliations: Department of Basic Oncology, Oncology Institute, Istanbul University, Capa 34390, Istanbul, Turkey, Institute of Clinical Chemistry and Pharmacology, University of Bonn, D-53127 Bonn, Germany
Pages: 1095-1098
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Published online on: February 10, 2012

https://doi.org/10.3892/ol.2012.600
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Abstract

Circulating DNA is present in plasma/serum, mainly complexed with histones as nucleosomes. The detection of circulating nucleosomes (cNUCs) in the peripheral blood may be a diagnostic modality for cancer-associated changes of modified histone tails in blood circulation. In the present study, we investigated the correlation between the trimethylation of H3 lysine 9 (H3K9me3) and H4 lysine 20 (H4K20me3), which are hallmarks of pericentric heterochromatin, and cNUCs in healthy subjects and patients with colorectal cancer (CRC) and multiple myeloma (MM). The plasma concentration of cNUCs was measured using the Cell-Death Detection ELISA kit. Histone methylation marks were detected using chromatin immunoprecipitation (ChIP), followed by quantitative PCR with pericentric satellite 2 as the target sequence. The results showed a high variation in the concentrations of cNUCs, with healthy subjects exhibiting the lowest levels (median 0.194), the CRC patients intermediate (median 0.25) and the MM patients the highest levels (median 0.648). However, the differences between the groups did not reach statistical significance (p>0.05). Analysis using the Pearson's correlation test revealed a significant positive correlation between the concentration of cNUCs and H3K9me3 and H4K20me3 in the whole study group (N=57, p<0.001 for both histone marks). A study of the correlation between cNUCs and histone marks in the individual study groups demonstrated the correlation between cNUCs and H3K9me3 in CRC patients to be weak (p=0.046), indicating that circulating H3K9me3 may be modified in CRC patients. The histone marks were normalized using the values of cNUCs. In agreement with the weak correlation between cNUCs and H3K9me3 in CRC patients, H3K9me3 levels (median 0.047) were lowest in this group compared with the other two groups (0.06 in healthy subjects, 0.2 in MM patients, p = not significant). For H4K20me3, the median values were 0.022 in healthy subjects, 0.052 in CRC patients and 0.056 in MM patients. In conclusion, our findings indicate a marked correlation between cNUCs and histone methyl marks.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

Molecular Medicine Reports

Oncology Reports

Experimental and Therapeutic Medicine

Oncology Letters

Biomedical Reports

Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Correlation of histone methyl marks with circulating nucleosomes in blood plasma of cancer patients

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