DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma
Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discove...
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| Veröffentlicht in: | Clinical epigenetics 2020-11, Vol.12 (1), p.163-163, Article 163 |
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| creator | Alberge, Jean-Baptiste Magrangeas, Florence Wagner, Mirko Denié, Soline Guérin-Charbonnel, Catherine Campion, Loïc Attal, Michel Avet-Loiseau, Hervé Carell, Thomas Moreau, Philippe Minvielle, Stéphane Sérandour, Aurélien A |
| description | Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play a role in tumor biology; however, little is known about its level and distribution in myeloma. In this study, we investigated the global level and the genomic localization of 5hmC in myeloma cells from 40 newly diagnosed patients, including paired relapses, and of control individuals.
Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P |
| doi_str_mv | 10.1186/s13148-020-00953-y |
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Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P < 0.001). Higher levels of 5hmC were found in lower grades of the International Staging System prognostic index (P < 0.05) and tend to associate with a longer overall survival (P < 0.1). From the hydroxymethylome data, we observed that the remaining 5hmC is organized in large domains overlapping with active chromatin marks and chromatin opening. We discovered that 5hmC strongly persists at key oncogenic genes such as CCND1, CCND2 and MMSET and characterized domains that are specifically hydroxymethylated in myeloma subgroups. Novel 5hmC-enriched domains were found at putative enhancers of CCND2 and MYC in newly diagnosed patients.
5hmC level is associated with clinical aspects of MM. Mapping 5hmC at a genome-wide level provides insights into the disease biology directly from genomic DNA, which makes it a potent mark to study epigenetics on large patient cohorts.</description><identifier>ISSN: 1868-7075</identifier><identifier>ISSN: 1868-7083</identifier><identifier>EISSN: 1868-7083</identifier><identifier>EISSN: 1868-7075</identifier><identifier>DOI: 10.1186/s13148-020-00953-y</identifier><identifier>PMID: 33138842</identifier><language>eng</language><publisher>Germany: BioMed Central Ltd</publisher><subject>Cancer ; Chromatin ; Clinical aspects ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Enhancers ; Epigenetic inheritance ; Epigenetics ; Gene mapping ; Genes ; Genomes ; Genomics ; Life Sciences ; Localization ; Malignancy ; Medical prognosis ; Medical research ; Multiple myeloma ; Myc protein ; Patients ; Phenotypes ; Plasma ; Plasma cells ; Stem cells ; Survival analysis</subject><ispartof>Clinical epigenetics, 2020-11, Vol.12 (1), p.163-163, Article 163</ispartof><rights>COPYRIGHT 2020 BioMed Central Ltd.</rights><rights>2020. This work is licensed under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>Distributed under a Creative Commons Attribution 4.0 International License</rights><rights>The Author(s) 2020</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c534t-42835352e51cde86f5fcca29ebefc5613127a199c25741cdb952909d3882086d3</citedby><cites>FETCH-LOGICAL-c534t-42835352e51cde86f5fcca29ebefc5613127a199c25741cdb952909d3882086d3</cites><orcidid>0000-0001-5253-9567 ; 0000-0002-4218-7294 ; 0000-0003-1389-312X ; 0000-0003-4903-0908 ; 0000-0002-3050-0140 ; 0000-0003-1780-8746</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607866/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7607866/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/33138842$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://inserm.hal.science/inserm-03006751$$DView record in HAL$$Hfree_for_read</backlink></links><search><creatorcontrib>Alberge, Jean-Baptiste</creatorcontrib><creatorcontrib>Magrangeas, Florence</creatorcontrib><creatorcontrib>Wagner, Mirko</creatorcontrib><creatorcontrib>Denié, Soline</creatorcontrib><creatorcontrib>Guérin-Charbonnel, Catherine</creatorcontrib><creatorcontrib>Campion, Loïc</creatorcontrib><creatorcontrib>Attal, Michel</creatorcontrib><creatorcontrib>Avet-Loiseau, Hervé</creatorcontrib><creatorcontrib>Carell, Thomas</creatorcontrib><creatorcontrib>Moreau, Philippe</creatorcontrib><creatorcontrib>Minvielle, Stéphane</creatorcontrib><creatorcontrib>Sérandour, Aurélien A</creatorcontrib><title>DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma</title><title>Clinical epigenetics</title><addtitle>Clin Epigenetics</addtitle><description>Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play a role in tumor biology; however, little is known about its level and distribution in myeloma. In this study, we investigated the global level and the genomic localization of 5hmC in myeloma cells from 40 newly diagnosed patients, including paired relapses, and of control individuals.
Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P < 0.001). Higher levels of 5hmC were found in lower grades of the International Staging System prognostic index (P < 0.05) and tend to associate with a longer overall survival (P < 0.1). From the hydroxymethylome data, we observed that the remaining 5hmC is organized in large domains overlapping with active chromatin marks and chromatin opening. We discovered that 5hmC strongly persists at key oncogenic genes such as CCND1, CCND2 and MMSET and characterized domains that are specifically hydroxymethylated in myeloma subgroups. Novel 5hmC-enriched domains were found at putative enhancers of CCND2 and MYC in newly diagnosed patients.
5hmC level is associated with clinical aspects of MM. Mapping 5hmC at a genome-wide level provides insights into the disease biology directly from genomic DNA, which makes it a potent mark to study epigenetics on large patient cohorts.</description><subject>Cancer</subject><subject>Chromatin</subject><subject>Clinical aspects</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Enhancers</subject><subject>Epigenetic inheritance</subject><subject>Epigenetics</subject><subject>Gene mapping</subject><subject>Genes</subject><subject>Genomes</subject><subject>Genomics</subject><subject>Life Sciences</subject><subject>Localization</subject><subject>Malignancy</subject><subject>Medical prognosis</subject><subject>Medical research</subject><subject>Multiple myeloma</subject><subject>Myc protein</subject><subject>Patients</subject><subject>Phenotypes</subject><subject>Plasma</subject><subject>Plasma cells</subject><subject>Stem cells</subject><subject>Survival analysis</subject><issn>1868-7075</issn><issn>1868-7083</issn><issn>1868-7083</issn><issn>1868-7075</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNptks1vFCEYxidGY5vaf8CDIfHiwal8DAxcTDb1oyYbveiZsMw7OzQzsAKzdQ7-71K3rrYRDhD4Pc8Lb56qek7wBSFSvEmEkUbWmOIaY8VZvTyqTsuFrFss2ePjvuUn1XlK17gMppQi-Gl1whhhUjb0tPr57vMKDUsXw49lgjwso8kueOQSMikF60yGDt24PKDOJTAJUII9RJcXZHyHdhCTS7nQGYEfjLflAIUeBW_DFryzKMK2OCbkPJrmMbvdCGhaYAyTeVY96c2Y4PxuPau-fXj_9fKqXn_5-Olyta4tZ02uGyoZZ5wCJ7YDKXreW2uogg30lovSCdoaopSlvG0KslGcKqy68keKpejYWfX24LubNxN0FnyOZtS76CYTFx2M0_dvvBv0Nux1K3ArhSgGrw8GwwPZ1WqtnU8QJ40ZxqLlZE8K_uquXgzfZ0hZTy5ZGEfjIcxJ04a3VArO24K-fIBehzn60o1CCUqJVIT9pbZmhFKwD-WZ9tZUr0RDqVSKqkJd_Icqs4PJ2eChd-X8noAeBDaGlCL0x78RrG9jpg8x0yVm-nfM9FJEL_5t5lHyJ1TsFzadznU</recordid><startdate>20201102</startdate><enddate>20201102</enddate><creator>Alberge, Jean-Baptiste</creator><creator>Magrangeas, Florence</creator><creator>Wagner, Mirko</creator><creator>Denié, Soline</creator><creator>Guérin-Charbonnel, Catherine</creator><creator>Campion, Loïc</creator><creator>Attal, Michel</creator><creator>Avet-Loiseau, Hervé</creator><creator>Carell, Thomas</creator><creator>Moreau, Philippe</creator><creator>Minvielle, Stéphane</creator><creator>Sérandour, Aurélien A</creator><general>BioMed Central Ltd</general><general>BioMed 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hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma</title><author>Alberge, Jean-Baptiste ; Magrangeas, Florence ; Wagner, Mirko ; Denié, Soline ; Guérin-Charbonnel, Catherine ; Campion, Loïc ; Attal, Michel ; Avet-Loiseau, Hervé ; Carell, Thomas ; Moreau, Philippe ; Minvielle, Stéphane ; Sérandour, Aurélien A</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c534t-42835352e51cde86f5fcca29ebefc5613127a199c25741cdb952909d3882086d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Cancer</topic><topic>Chromatin</topic><topic>Clinical aspects</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Enhancers</topic><topic>Epigenetic inheritance</topic><topic>Epigenetics</topic><topic>Gene mapping</topic><topic>Genes</topic><topic>Genomes</topic><topic>Genomics</topic><topic>Life Sciences</topic><topic>Localization</topic><topic>Malignancy</topic><topic>Medical prognosis</topic><topic>Medical research</topic><topic>Multiple myeloma</topic><topic>Myc protein</topic><topic>Patients</topic><topic>Phenotypes</topic><topic>Plasma</topic><topic>Plasma cells</topic><topic>Stem cells</topic><topic>Survival analysis</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Alberge, Jean-Baptiste</creatorcontrib><creatorcontrib>Magrangeas, Florence</creatorcontrib><creatorcontrib>Wagner, Mirko</creatorcontrib><creatorcontrib>Denié, Soline</creatorcontrib><creatorcontrib>Guérin-Charbonnel, Catherine</creatorcontrib><creatorcontrib>Campion, Loïc</creatorcontrib><creatorcontrib>Attal, Michel</creatorcontrib><creatorcontrib>Avet-Loiseau, Hervé</creatorcontrib><creatorcontrib>Carell, Thomas</creatorcontrib><creatorcontrib>Moreau, 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Academic</collection><collection>Hyper Article en Ligne (HAL)</collection><collection>Hyper Article en Ligne (HAL) (Open Access)</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Clinical epigenetics</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Alberge, Jean-Baptiste</au><au>Magrangeas, Florence</au><au>Wagner, Mirko</au><au>Denié, Soline</au><au>Guérin-Charbonnel, Catherine</au><au>Campion, Loïc</au><au>Attal, Michel</au><au>Avet-Loiseau, Hervé</au><au>Carell, Thomas</au><au>Moreau, Philippe</au><au>Minvielle, Stéphane</au><au>Sérandour, Aurélien A</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma</atitle><jtitle>Clinical epigenetics</jtitle><addtitle>Clin Epigenetics</addtitle><date>2020-11-02</date><risdate>2020</risdate><volume>12</volume><issue>1</issue><spage>163</spage><epage>163</epage><pages>163-163</pages><artnum>163</artnum><issn>1868-7075</issn><issn>1868-7083</issn><eissn>1868-7083</eissn><eissn>1868-7075</eissn><abstract>Multiple myeloma (MM) is a heterogeneous plasma cell malignancy that remains challenging to cure. Global hypomethylation correlates with an aggressive phenotype of the disease, while hypermethylation is observed at particular regions of myeloma such as B cell-specific enhancers. The recently discovered active epigenetic mark 5-hydroxymethylCytosine (5hmC) may also play a role in tumor biology; however, little is known about its level and distribution in myeloma. In this study, we investigated the global level and the genomic localization of 5hmC in myeloma cells from 40 newly diagnosed patients, including paired relapses, and of control individuals.
Compared to normal plasma cells, we found global 5hmC levels to be lower in myeloma (P < 0.001). Higher levels of 5hmC were found in lower grades of the International Staging System prognostic index (P < 0.05) and tend to associate with a longer overall survival (P < 0.1). From the hydroxymethylome data, we observed that the remaining 5hmC is organized in large domains overlapping with active chromatin marks and chromatin opening. We discovered that 5hmC strongly persists at key oncogenic genes such as CCND1, CCND2 and MMSET and characterized domains that are specifically hydroxymethylated in myeloma subgroups. Novel 5hmC-enriched domains were found at putative enhancers of CCND2 and MYC in newly diagnosed patients.
5hmC level is associated with clinical aspects of MM. Mapping 5hmC at a genome-wide level provides insights into the disease biology directly from genomic DNA, which makes it a potent mark to study epigenetics on large patient cohorts.</abstract><cop>Germany</cop><pub>BioMed Central Ltd</pub><pmid>33138842</pmid><doi>10.1186/s13148-020-00953-y</doi><tpages>1</tpages><orcidid>https://orcid.org/0000-0001-5253-9567</orcidid><orcidid>https://orcid.org/0000-0002-4218-7294</orcidid><orcidid>https://orcid.org/0000-0003-1389-312X</orcidid><orcidid>https://orcid.org/0000-0003-4903-0908</orcidid><orcidid>https://orcid.org/0000-0002-3050-0140</orcidid><orcidid>https://orcid.org/0000-0003-1780-8746</orcidid><oa>free_for_read</oa></addata></record> |
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| subjects | Cancer Chromatin Clinical aspects Deoxyribonucleic acid DNA DNA methylation Enhancers Epigenetic inheritance Epigenetics Gene mapping Genes Genomes Genomics Life Sciences Localization Malignancy Medical prognosis Medical research Multiple myeloma Myc protein Patients Phenotypes Plasma Plasma cells Stem cells Survival analysis |
| title | DNA hydroxymethylation is associated with disease severity and persists at enhancers of oncogenic regions in multiple myeloma |
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