An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma
Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, t...
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| Veröffentlicht in: | PloS one 2012-09, Vol.7 (9), p.e44997 |
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| creator | Watkins, A James Hamoudi, Rifat A Zeng, Naiyan Yan, Qingguo Huang, Yuanxue Liu, Hongxiang Zhang, Jianzhong Braggio, Esteban Fonseca, Rafael de Leval, Laurence Isaacson, Peter G Wotherspoon, Andrew McPhail, Ellen D Dogan, Ahmet Du, Ming-Qing |
| description | Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P |
| doi_str_mv | 10.1371/journal.pone.0044997 |
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In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P<0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. These observations provide valuable guidance for further characterisation of 7q deletion.</description><identifier>ISSN: 1932-6203</identifier><identifier>EISSN: 1932-6203</identifier><identifier>DOI: 10.1371/journal.pone.0044997</identifier><identifier>PMID: 23028731</identifier><language>eng</language><publisher>United States: Public Library of Science</publisher><subject>Artificial chromosomes ; Biology ; Cancer ; Chromosome Deletion ; Chromosomes, Human, Pair 7 - genetics ; Clonal deletion ; Comparative analysis ; Comparative Genomic Hybridization ; Cytogenetics ; Deoxyribonucleic acid ; DNA ; DNA methylation ; Epigenesis, Genetic ; Epigenetic inheritance ; Gene deletion ; Gene expression ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene sequencing ; Genes ; Genes, Neoplasm - genetics ; Genetic analysis ; Genetic aspects ; Genome, Human - genetics ; Genomics ; Heterozygote ; Histopathology ; Humans ; Hybridization ; Interferon Regulatory Factors - genetics ; Laboratories ; Lymphocytes ; Lymphocytes B ; Lymphoma ; Lymphoma, B-Cell, Marginal Zone - genetics ; Medicine ; MicroRNA ; MicroRNAs ; MicroRNAs - genetics ; MicroRNAs - metabolism ; miRNA ; Mutation ; Mutation - genetics ; Non-Hodgkin's lymphomas ; Oligonucleotide Array Sequence Analysis ; Open Reading Frames - genetics ; Pathology ; Polymorphism, Genetic ; Prostate ; Reverse Transcriptase Polymerase Chain Reaction ; Sequence Analysis, DNA ; Sequence Analysis, RNA ; Skin cancer ; Spleen ; Splenic Neoplasms - genetics ; Studies</subject><ispartof>PloS one, 2012-09, Vol.7 (9), p.e44997</ispartof><rights>COPYRIGHT 2012 Public Library of Science</rights><rights>Watkins et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License: https://creativecommons.org/licenses/by/4.0/ (the “License”), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2012 Watkins et al 2012 Watkins et al</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c692t-ec10bcf89721b96c34b6c9c9eaa78fd86adc63bac5f155f69df906d780f2bf183</citedby></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441634/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC3441634/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,723,776,780,860,881,2096,2915,23845,27901,27902,53766,53768,79342,79343</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/23028731$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Watkins, A James</creatorcontrib><creatorcontrib>Hamoudi, Rifat A</creatorcontrib><creatorcontrib>Zeng, Naiyan</creatorcontrib><creatorcontrib>Yan, Qingguo</creatorcontrib><creatorcontrib>Huang, Yuanxue</creatorcontrib><creatorcontrib>Liu, Hongxiang</creatorcontrib><creatorcontrib>Zhang, Jianzhong</creatorcontrib><creatorcontrib>Braggio, Esteban</creatorcontrib><creatorcontrib>Fonseca, Rafael</creatorcontrib><creatorcontrib>de Leval, Laurence</creatorcontrib><creatorcontrib>Isaacson, Peter G</creatorcontrib><creatorcontrib>Wotherspoon, Andrew</creatorcontrib><creatorcontrib>McPhail, Ellen D</creatorcontrib><creatorcontrib>Dogan, Ahmet</creatorcontrib><creatorcontrib>Du, Ming-Qing</creatorcontrib><title>An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma</title><title>PloS one</title><addtitle>PLoS One</addtitle><description>Splenic marginal zone lymphoma (SMZL) is an indolent B-cell lymphoproliferative disorder characterised by 7q32 deletion, but the target genes of this deletion remain unknown. In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P<0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. These observations provide valuable guidance for further characterisation of 7q deletion.</description><subject>Artificial chromosomes</subject><subject>Biology</subject><subject>Cancer</subject><subject>Chromosome Deletion</subject><subject>Chromosomes, Human, Pair 7 - genetics</subject><subject>Clonal deletion</subject><subject>Comparative analysis</subject><subject>Comparative Genomic Hybridization</subject><subject>Cytogenetics</subject><subject>Deoxyribonucleic acid</subject><subject>DNA</subject><subject>DNA methylation</subject><subject>Epigenesis, Genetic</subject><subject>Epigenetic inheritance</subject><subject>Gene deletion</subject><subject>Gene expression</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene sequencing</subject><subject>Genes</subject><subject>Genes, Neoplasm - genetics</subject><subject>Genetic analysis</subject><subject>Genetic aspects</subject><subject>Genome, Human - genetics</subject><subject>Genomics</subject><subject>Heterozygote</subject><subject>Histopathology</subject><subject>Humans</subject><subject>Hybridization</subject><subject>Interferon Regulatory Factors - genetics</subject><subject>Laboratories</subject><subject>Lymphocytes</subject><subject>Lymphocytes B</subject><subject>Lymphoma</subject><subject>Lymphoma, B-Cell, Marginal Zone - genetics</subject><subject>Medicine</subject><subject>MicroRNA</subject><subject>MicroRNAs</subject><subject>MicroRNAs - genetics</subject><subject>MicroRNAs - metabolism</subject><subject>miRNA</subject><subject>Mutation</subject><subject>Mutation - genetics</subject><subject>Non-Hodgkin's lymphomas</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Open Reading Frames - genetics</subject><subject>Pathology</subject><subject>Polymorphism, Genetic</subject><subject>Prostate</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Sequence Analysis, DNA</subject><subject>Sequence Analysis, RNA</subject><subject>Skin cancer</subject><subject>Spleen</subject><subject>Splenic Neoplasms - genetics</subject><subject>Studies</subject><issn>1932-6203</issn><issn>1932-6203</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2012</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><sourceid>BENPR</sourceid><sourceid>DOA</sourceid><recordid>eNqNkl2L1DAUhoso7rr6D0QLguDFjEnTJs2NMCx-DCws-HVpSJOTToY06TYd2fHXm3G6yxQUJBdNT573zeHkzbLnGC0xYfjtNuwGL92yDx6WCJUl5-xBdo45KRa0QOThyf4sexLjFqGK1JQ-zs4KgoqaEXye_Vj53PoR2kGOoPMWfOisyqXXOdz2A8Rog0-_0u2jjXkwObvJNTgYD3Xr89g78EnRyaG1Cct_pX5yt-_6Tejk0-yRkS7Cs-l7kX378P7r5afF1fXH9eXqaqEoL8YFKIwaZWrOCtxwqkjZUMUVBylZbXRNpVaUNFJVBleVoVwbjqhmNTJFY3BNLrKXR9_ehSim0USBSUGrsi4QSsT6SOggt6IfbGp4L4K04k8hDK2Qw2iVAwFYlxKwQozSEtKecd1wRomuEE3XJa930227pgOtwI-DdDPT-Ym3G9GGn4KUJaakTAavJoMh3Owgjv9oeaJambqy3oRkpjoblVhVJSGYVTVP1PIvVFoa0kumxzA21WeCNzNBYka4HVu5i1Gsv3z-f_b6-5x9fcJuQLpxE4PbHZIS52B5BNUQYhzA3E8OI3HI9t00xCHbYsp2kr04nfq96C7M5DfBqPXE</recordid><startdate>20120913</startdate><enddate>20120913</enddate><creator>Watkins, A James</creator><creator>Hamoudi, Rifat A</creator><creator>Zeng, Naiyan</creator><creator>Yan, Qingguo</creator><creator>Huang, Yuanxue</creator><creator>Liu, Hongxiang</creator><creator>Zhang, Jianzhong</creator><creator>Braggio, Esteban</creator><creator>Fonseca, Rafael</creator><creator>de Leval, Laurence</creator><creator>Isaacson, Peter G</creator><creator>Wotherspoon, Andrew</creator><creator>McPhail, Ellen D</creator><creator>Dogan, Ahmet</creator><creator>Du, Ming-Qing</creator><general>Public Library of Science</general><general>Public Library of Science (PLoS)</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>IOV</scope><scope>ISR</scope><scope>3V.</scope><scope>7QG</scope><scope>7QL</scope><scope>7QO</scope><scope>7RV</scope><scope>7SN</scope><scope>7SS</scope><scope>7T5</scope><scope>7TG</scope><scope>7TM</scope><scope>7U9</scope><scope>7X2</scope><scope>7X7</scope><scope>7XB</scope><scope>88E</scope><scope>8AO</scope><scope>8C1</scope><scope>8FD</scope><scope>8FE</scope><scope>8FG</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABJCF</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>ARAPS</scope><scope>ATCPS</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BGLVJ</scope><scope>BHPHI</scope><scope>C1K</scope><scope>CCPQU</scope><scope>D1I</scope><scope>DWQXO</scope><scope>FR3</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>H94</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>KB.</scope><scope>KB0</scope><scope>KL.</scope><scope>L6V</scope><scope>LK8</scope><scope>M0K</scope><scope>M0S</scope><scope>M1P</scope><scope>M7N</scope><scope>M7P</scope><scope>M7S</scope><scope>NAPCQ</scope><scope>P5Z</scope><scope>P62</scope><scope>P64</scope><scope>PATMY</scope><scope>PDBOC</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>PTHSS</scope><scope>PYCSY</scope><scope>RC3</scope><scope>5PM</scope><scope>DOA</scope></search><sort><creationdate>20120913</creationdate><title>An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma</title><author>Watkins, A James ; Hamoudi, Rifat A ; Zeng, Naiyan ; Yan, Qingguo ; Huang, Yuanxue ; Liu, Hongxiang ; Zhang, Jianzhong ; Braggio, Esteban ; Fonseca, Rafael ; de Leval, Laurence ; Isaacson, Peter G ; Wotherspoon, Andrew ; McPhail, Ellen D ; Dogan, Ahmet ; Du, Ming-Qing</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c692t-ec10bcf89721b96c34b6c9c9eaa78fd86adc63bac5f155f69df906d780f2bf183</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2012</creationdate><topic>Artificial chromosomes</topic><topic>Biology</topic><topic>Cancer</topic><topic>Chromosome Deletion</topic><topic>Chromosomes, Human, Pair 7 - genetics</topic><topic>Clonal deletion</topic><topic>Comparative analysis</topic><topic>Comparative Genomic Hybridization</topic><topic>Cytogenetics</topic><topic>Deoxyribonucleic acid</topic><topic>DNA</topic><topic>DNA methylation</topic><topic>Epigenesis, Genetic</topic><topic>Epigenetic inheritance</topic><topic>Gene deletion</topic><topic>Gene expression</topic><topic>Gene Expression Profiling</topic><topic>Gene Expression Regulation, Neoplastic</topic><topic>Gene sequencing</topic><topic>Genes</topic><topic>Genes, Neoplasm - genetics</topic><topic>Genetic analysis</topic><topic>Genetic aspects</topic><topic>Genome, Human - genetics</topic><topic>Genomics</topic><topic>Heterozygote</topic><topic>Histopathology</topic><topic>Humans</topic><topic>Hybridization</topic><topic>Interferon Regulatory Factors - genetics</topic><topic>Laboratories</topic><topic>Lymphocytes</topic><topic>Lymphocytes B</topic><topic>Lymphoma</topic><topic>Lymphoma, B-Cell, Marginal Zone - genetics</topic><topic>Medicine</topic><topic>MicroRNA</topic><topic>MicroRNAs</topic><topic>MicroRNAs - 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In order to elucidate the genetic target of this deletion, we performed an integrative analysis of the genetic, epigenetic, transcriptomic and miRNomic data. High resolution array comparative genomic hybridization of 56 cases of SMZL delineated a minimally deleted region (2.8 Mb) at 7q32, but showed no evidence of any cryptic homozygous deletion or recurrent breakpoint in this region. Integrated transcriptomic analysis confirmed significant under-expression of a number of genes in this region in cases of SMZL with deletion, several of which showed hypermethylation. In addition, a cluster of 8 miRNA in this region showed under-expression in cases with the deletion, and three (miR-182/96/183) were also significantly under-expressed (P<0.05) in SMZL relative to other lymphomas. Genomic sequencing of these miRNA and IRF5, a strong candidate gene, did not show any evidence of somatic mutation in SMZL. These observations provide valuable guidance for further characterisation of 7q deletion.</abstract><cop>United States</cop><pub>Public Library of Science</pub><pmid>23028731</pmid><doi>10.1371/journal.pone.0044997</doi><tpages>e44997</tpages><oa>free_for_read</oa></addata></record> |
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| ispartof | PloS one, 2012-09, Vol.7 (9), p.e44997 |
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| source | Public Library of Science (PLoS) Journals Open Access; MEDLINE; DOAJ Directory of Open Access Journals; Free E-Journal (出版社公開部分のみ）; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | Artificial chromosomes Biology Cancer Chromosome Deletion Chromosomes, Human, Pair 7 - genetics Clonal deletion Comparative analysis Comparative Genomic Hybridization Cytogenetics Deoxyribonucleic acid DNA DNA methylation Epigenesis, Genetic Epigenetic inheritance Gene deletion Gene expression Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene sequencing Genes Genes, Neoplasm - genetics Genetic analysis Genetic aspects Genome, Human - genetics Genomics Heterozygote Histopathology Humans Hybridization Interferon Regulatory Factors - genetics Laboratories Lymphocytes Lymphocytes B Lymphoma Lymphoma, B-Cell, Marginal Zone - genetics Medicine MicroRNA MicroRNAs MicroRNAs - genetics MicroRNAs - metabolism miRNA Mutation Mutation - genetics Non-Hodgkin's lymphomas Oligonucleotide Array Sequence Analysis Open Reading Frames - genetics Pathology Polymorphism, Genetic Prostate Reverse Transcriptase Polymerase Chain Reaction Sequence Analysis, DNA Sequence Analysis, RNA Skin cancer Spleen Splenic Neoplasms - genetics Studies |
| title | An integrated genomic and expression analysis of 7q deletion in splenic marginal zone lymphoma |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-12T05%3A14%3A08IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_plos_&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20integrated%20genomic%20and%20expression%20analysis%20of%207q%20deletion%20in%20splenic%20marginal%20zone%20lymphoma&rft.jtitle=PloS%20one&rft.au=Watkins,%20A%20James&rft.date=2012-09-13&rft.volume=7&rft.issue=9&rft.spage=e44997&rft.pages=e44997-&rft.issn=1932-6203&rft.eissn=1932-6203&rft_id=info:doi/10.1371/journal.pone.0044997&rft_dat=%3Cgale_plos_%3EA543317589%3C/gale_plos_%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1326548200&rft_id=info:pmid/23028731&rft_galeid=A543317589&rft_doaj_id=oai_doaj_org_article_e1d4ae1c07664ed4a79db9763d506bf1&rfr_iscdi=true |