Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients
Secondary MYC translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identifie...
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| Veröffentlicht in: | Blood cancer journal (New York) 2014-03, Vol.4 (3), p.e191-e191 |
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| creator | Walker, B A Wardell, C P Brioli, A Boyle, E Kaiser, M F Begum, D B Dahir, N B Johnson, D C Ross, F M Davies, F E Morgan, G J |
| description | Secondary
MYC
translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including
IGH
,
IGK
and
IGL
, which juxtapose the immunoglobulin (Ig) enhancers next to
MYC
in 8/23 samples. The remaining samples had partner loci including
XBP1
,
FAM46C
,
CCND1
and
KRAS
, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of
MYC
in these samples. Patients with
MYC
translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near
MYC
result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of
MYC
and an aggressive disease phenotype. |
| doi_str_mv | 10.1038/bcj.2014.13 |
| format | Article |
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MYC
translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including
IGH
,
IGK
and
IGL
, which juxtapose the immunoglobulin (Ig) enhancers next to
MYC
in 8/23 samples. The remaining samples had partner loci including
XBP1
,
FAM46C
,
CCND1
and
KRAS
, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of
MYC
in these samples. Patients with
MYC
translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near
MYC
result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of
MYC
and an aggressive disease phenotype.</description><identifier>ISSN: 2044-5385</identifier><identifier>EISSN: 2044-5385</identifier><identifier>DOI: 10.1038/bcj.2014.13</identifier><identifier>PMID: 24632883</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>692/420/2489/68 ; 692/699/67/1990/804 ; Biomedical and Life Sciences ; Biomedicine ; Cancer Research ; Hematology ; Oncology ; Original ; original-article</subject><ispartof>Blood cancer journal (New York), 2014-03, Vol.4 (3), p.e191-e191</ispartof><rights>The Author(s) 2014</rights><rights>Copyright Nature Publishing Group Mar 2014</rights><rights>Copyright © 2014 Macmillan Publishers Limited 2014 Macmillan Publishers Limited</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c446t-422aa57cde258d1a81ec130531fa0df9b0d5e51ebd2f77396724a918920e3e9f3</citedby><cites>FETCH-LOGICAL-c446t-422aa57cde258d1a81ec130531fa0df9b0d5e51ebd2f77396724a918920e3e9f3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972699/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3972699/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/24632883$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Walker, B A</creatorcontrib><creatorcontrib>Wardell, C P</creatorcontrib><creatorcontrib>Brioli, A</creatorcontrib><creatorcontrib>Boyle, E</creatorcontrib><creatorcontrib>Kaiser, M F</creatorcontrib><creatorcontrib>Begum, D B</creatorcontrib><creatorcontrib>Dahir, N B</creatorcontrib><creatorcontrib>Johnson, D C</creatorcontrib><creatorcontrib>Ross, F M</creatorcontrib><creatorcontrib>Davies, F E</creatorcontrib><creatorcontrib>Morgan, G J</creatorcontrib><title>Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients</title><title>Blood cancer journal (New York)</title><addtitle>Blood Cancer Journal</addtitle><addtitle>Blood Cancer J</addtitle><description>Secondary
MYC
translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including
IGH
,
IGK
and
IGL
, which juxtapose the immunoglobulin (Ig) enhancers next to
MYC
in 8/23 samples. The remaining samples had partner loci including
XBP1
,
FAM46C
,
CCND1
and
KRAS
, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of
MYC
in these samples. Patients with
MYC
translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near
MYC
result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of
MYC
and an aggressive disease phenotype.</description><subject>692/420/2489/68</subject><subject>692/699/67/1990/804</subject><subject>Biomedical and Life Sciences</subject><subject>Biomedicine</subject><subject>Cancer Research</subject><subject>Hematology</subject><subject>Oncology</subject><subject>Original</subject><subject>original-article</subject><issn>2044-5385</issn><issn>2044-5385</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><recordid>eNptkUtv1DAUhSMEaqvSVffIEhskmMGvJPYGCY2gRWrVTVmwshzn5jFK7NQ3Ke2P4D_j0ZRqQHhjy-fzOdc6WXbO6JpRoT5WbrvmlMk1Ey-yE06lXOVC5S8PzsfZGeKWppUXTDN9lB1zWQiulDjJft1G63EIzs598EjsTNQdl2S7PMx2Cgjk-seG_OznjrTgAcncJaSzsQqR4DJBBN9Z7yAiiYDLMPe-Jb0n4T5JD1O6w2RMrK_JFNKbKYbWB-xxB42PMITRkimlg5_xdfaqsQPC2dN-mn3_-uV2c7m6urn4tvl8tXJSFvNKcm5tXroaeK5qZhUDxwTNBWssrRtd0TqHnEFV86YshS5KLq1mSnMKAnQjTrNPe99pqUaoXcqOdjBT7EcbH02wvflb8X1n2nBvhC55oXUyePdkEMPdAjibsUcHw2A9hAUNy6mSTArOE_r2H3QblujT9wwrldSCs6JM1Ps95WJAjNA8D8Oo2TVtUtNm17RhItFvDud_Zv_0moAPewCT5FuIB6H_8fsN6RC2Lw</recordid><startdate>20140314</startdate><enddate>20140314</enddate><creator>Walker, B A</creator><creator>Wardell, C P</creator><creator>Brioli, A</creator><creator>Boyle, E</creator><creator>Kaiser, M F</creator><creator>Begum, D B</creator><creator>Dahir, N B</creator><creator>Johnson, D C</creator><creator>Ross, F M</creator><creator>Davies, F E</creator><creator>Morgan, G J</creator><general>Nature Publishing Group UK</general><general>Springer Nature B.V</general><general>Nature Publishing Group</general><scope>C6C</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BENPR</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>K9.</scope><scope>M0S</scope><scope>M1P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PRINS</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20140314</creationdate><title>Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients</title><author>Walker, B A ; Wardell, C P ; Brioli, A ; Boyle, E ; Kaiser, M F ; Begum, D B ; Dahir, N B ; Johnson, D C ; Ross, F M ; Davies, F E ; Morgan, G J</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c446t-422aa57cde258d1a81ec130531fa0df9b0d5e51ebd2f77396724a918920e3e9f3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>692/420/2489/68</topic><topic>692/699/67/1990/804</topic><topic>Biomedical and Life Sciences</topic><topic>Biomedicine</topic><topic>Cancer Research</topic><topic>Hematology</topic><topic>Oncology</topic><topic>Original</topic><topic>original-article</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Walker, B A</creatorcontrib><creatorcontrib>Wardell, C P</creatorcontrib><creatorcontrib>Brioli, A</creatorcontrib><creatorcontrib>Boyle, E</creatorcontrib><creatorcontrib>Kaiser, M F</creatorcontrib><creatorcontrib>Begum, D B</creatorcontrib><creatorcontrib>Dahir, N B</creatorcontrib><creatorcontrib>Johnson, D C</creatorcontrib><creatorcontrib>Ross, F M</creatorcontrib><creatorcontrib>Davies, F E</creatorcontrib><creatorcontrib>Morgan, G J</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>ProQuest Central</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Access via ProQuest (Open Access)</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central China</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Blood cancer journal (New York)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Walker, B A</au><au>Wardell, C P</au><au>Brioli, A</au><au>Boyle, E</au><au>Kaiser, M F</au><au>Begum, D B</au><au>Dahir, N B</au><au>Johnson, D C</au><au>Ross, F M</au><au>Davies, F E</au><au>Morgan, G J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients</atitle><jtitle>Blood cancer journal (New York)</jtitle><stitle>Blood Cancer Journal</stitle><addtitle>Blood Cancer J</addtitle><date>2014-03-14</date><risdate>2014</risdate><volume>4</volume><issue>3</issue><spage>e191</spage><epage>e191</epage><pages>e191-e191</pages><issn>2044-5385</issn><eissn>2044-5385</eissn><abstract>Secondary
MYC
translocations in myeloma have been shown to be important in the pathogenesis and progression of disease. Here, we have used a DNA capture and massively parallel sequencing approach to identify the partner chromosomes in 104 presentation myeloma samples. 8q24 breakpoints were identified in 21 (20%) samples with partner loci including
IGH
,
IGK
and
IGL
, which juxtapose the immunoglobulin (Ig) enhancers next to
MYC
in 8/23 samples. The remaining samples had partner loci including
XBP1
,
FAM46C
,
CCND1
and
KRAS
, which are important in B-cell maturation or myeloma pathogenesis. Analysis of the region surrounding the breakpoints indicated the presence of superenhancers on the partner chromosomes and gene expression analysis showed increased expression of
MYC
in these samples. Patients with
MYC
translocations had a decreased progression-free and overall survival. We postulate that translocation breakpoints near
MYC
result in colocalization of the gene with superenhancers from loci, which are important in the development of the cell type in which they occur. In the case of myeloma these are the Ig loci and those important for plasma cell development and myeloma pathogenesis, resulting in increased expression of
MYC
and an aggressive disease phenotype.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>24632883</pmid><doi>10.1038/bcj.2014.13</doi><oa>free_for_read</oa></addata></record> |
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| identifier | ISSN: 2044-5385 |
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| source | DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central |
| subjects | 692/420/2489/68 692/699/67/1990/804 Biomedical and Life Sciences Biomedicine Cancer Research Hematology Oncology Original original-article |
| title | Translocations at 8q24 juxtapose MYC with genes that harbor superenhancers resulting in overexpression and poor prognosis in myeloma patients |
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