| Correlation of histone methyl marks with circulating nucleosomes in blood plasma of cancer patients. | |
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MedLine Citation:
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PMID: 22783398 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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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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Authors:
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Ugur Gezer; Ufuk Mert; Emre Ozgür; Ebru E Yörüker; Stefan Holdenrieder; Nejat Dalay |
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Publication Detail:
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Type: JOURNAL ARTICLE Date: 2012-2-10 |
Journal Detail:
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Title: Oncology letters Volume: 3 ISSN: 1792-1082 ISO Abbreviation: - Publication Date: 2012 May |
Date Detail:
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Created Date: 2012-7-11 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 101531236 Medline TA: Oncol Lett Country: - |
Other Details:
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Languages: ENG Pagination: 1095-1098 Citation Subset: - |
Affiliation:
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Department of Basic Oncology, Oncology Institute, Istanbul University, Capa 34390, Istanbul, Turkey. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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