An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes
Richard Gilbertson and colleagues report an in vivo screen of 84 candidate oncogenes and 39 candidate tumor-suppressor genes in ependymoma mouse models. The validated targets are involved in vesicle trafficking, DNA modification and cholesterol biosynthesis. Cancers are characterized by non-random c...
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| Veröffentlicht in: | Nature genetics 2015-08, Vol.47 (8), p.878-887 |
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| creator | Mohankumar, Kumarasamypet M Currle, David S White, Elsie Boulos, Nidal Dapper, Jason Eden, Christopher Nimmervoll, Birgit Thiruvenkatam, Radhika Connelly, Michele Kranenburg, Tanya A Neale, Geoffrey Olsen, Scott Wang, Yong-Dong Finkelstein, David Wright, Karen Gupta, Kirti Ellison, David W Thomas, Arzu Onar Gilbertson, Richard J |
| description | Richard Gilbertson and colleagues report an
in vivo
screen of 84 candidate oncogenes and 39 candidate tumor-suppressor genes in ependymoma mouse models. The validated targets are involved in vesicle trafficking, DNA modification and cholesterol biosynthesis.
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species
in vivo
screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets. |
| doi_str_mv | 10.1038/ng.3323 |
| format | Article |
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in vivo
screen of 84 candidate oncogenes and 39 candidate tumor-suppressor genes in ependymoma mouse models. The validated targets are involved in vesicle trafficking, DNA modification and cholesterol biosynthesis.
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species
in vivo
screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.</description><identifier>ISSN: 1061-4036</identifier><identifier>EISSN: 1546-1718</identifier><identifier>DOI: 10.1038/ng.3323</identifier><identifier>PMID: 26075792</identifier><language>eng</language><publisher>New York: Nature Publishing Group US</publisher><subject>14 ; 14/19 ; 14/34 ; 14/5 ; 45/100 ; 45/22 ; 45/61 ; 59/5 ; 631/114/2785 ; 631/1647/245 ; 631/80 ; 64/60 ; 692/699/67/1922 ; Agriculture ; Animal Genetics and Genomics ; Animals ; Biomedicine ; Biosynthesis ; Cancer ; Cancer Research ; Carcinogenesis ; Cells, Cultured ; Chromosome Aberrations ; Chromosomes ; Copy number variations ; DNA Copy Number Variations ; Ependymoma - genetics ; Ependymoma - metabolism ; Female ; Gene Expression Profiling ; Gene Expression Regulation, Neoplastic ; Gene Function ; Genes ; Genes, Tumor Suppressor ; Genetic aspects ; Genetic Predisposition to Disease - genetics ; HEK293 Cells ; Human Genetics ; Humans ; Identification and classification ; Kaplan-Meier Estimate ; Male ; Mice, Nude ; Mice, Transgenic ; Microscopy, Confocal ; Mutation ; Neoplasms, Experimental - genetics ; Neoplasms, Experimental - metabolism ; Neural Stem Cells - metabolism ; Neural Stem Cells - transplantation ; Oligonucleotide Array Sequence Analysis ; Oncogenes ; Oncogenes - genetics ; Properties ; Reverse Transcriptase Polymerase Chain Reaction ; Transfection ; Tumor suppressor genes ; Tumors</subject><ispartof>Nature genetics, 2015-08, Vol.47 (8), p.878-887</ispartof><rights>Springer Nature America, Inc. 2015</rights><rights>COPYRIGHT 2015 Nature Publishing Group</rights><rights>Copyright Nature Publishing Group Aug 2015</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c635t-a000ceb9b4e416bc8ad2a0698e4607f936c137956f954c043afa1b22296e0e323</citedby><cites>FETCH-LOGICAL-c635t-a000ceb9b4e416bc8ad2a0698e4607f936c137956f954c043afa1b22296e0e323</cites><orcidid>0000-0002-5329-4968 ; 0000000253294968</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,780,784,885,27924,27925</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26075792$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Mohankumar, Kumarasamypet M</creatorcontrib><creatorcontrib>Currle, David S</creatorcontrib><creatorcontrib>White, Elsie</creatorcontrib><creatorcontrib>Boulos, Nidal</creatorcontrib><creatorcontrib>Dapper, Jason</creatorcontrib><creatorcontrib>Eden, Christopher</creatorcontrib><creatorcontrib>Nimmervoll, Birgit</creatorcontrib><creatorcontrib>Thiruvenkatam, Radhika</creatorcontrib><creatorcontrib>Connelly, Michele</creatorcontrib><creatorcontrib>Kranenburg, Tanya A</creatorcontrib><creatorcontrib>Neale, Geoffrey</creatorcontrib><creatorcontrib>Olsen, Scott</creatorcontrib><creatorcontrib>Wang, Yong-Dong</creatorcontrib><creatorcontrib>Finkelstein, David</creatorcontrib><creatorcontrib>Wright, Karen</creatorcontrib><creatorcontrib>Gupta, Kirti</creatorcontrib><creatorcontrib>Ellison, David W</creatorcontrib><creatorcontrib>Thomas, Arzu Onar</creatorcontrib><creatorcontrib>Gilbertson, Richard J</creatorcontrib><title>An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes</title><title>Nature genetics</title><addtitle>Nat Genet</addtitle><addtitle>Nat Genet</addtitle><description>Richard Gilbertson and colleagues report an
in vivo
screen of 84 candidate oncogenes and 39 candidate tumor-suppressor genes in ependymoma mouse models. The validated targets are involved in vesicle trafficking, DNA modification and cholesterol biosynthesis.
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species
in vivo
screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.</description><subject>14</subject><subject>14/19</subject><subject>14/34</subject><subject>14/5</subject><subject>45/100</subject><subject>45/22</subject><subject>45/61</subject><subject>59/5</subject><subject>631/114/2785</subject><subject>631/1647/245</subject><subject>631/80</subject><subject>64/60</subject><subject>692/699/67/1922</subject><subject>Agriculture</subject><subject>Animal Genetics and Genomics</subject><subject>Animals</subject><subject>Biomedicine</subject><subject>Biosynthesis</subject><subject>Cancer</subject><subject>Cancer Research</subject><subject>Carcinogenesis</subject><subject>Cells, Cultured</subject><subject>Chromosome Aberrations</subject><subject>Chromosomes</subject><subject>Copy number variations</subject><subject>DNA Copy Number Variations</subject><subject>Ependymoma - genetics</subject><subject>Ependymoma - metabolism</subject><subject>Female</subject><subject>Gene Expression Profiling</subject><subject>Gene Expression Regulation, Neoplastic</subject><subject>Gene Function</subject><subject>Genes</subject><subject>Genes, Tumor Suppressor</subject><subject>Genetic aspects</subject><subject>Genetic Predisposition to Disease - genetics</subject><subject>HEK293 Cells</subject><subject>Human Genetics</subject><subject>Humans</subject><subject>Identification and classification</subject><subject>Kaplan-Meier Estimate</subject><subject>Male</subject><subject>Mice, Nude</subject><subject>Mice, Transgenic</subject><subject>Microscopy, Confocal</subject><subject>Mutation</subject><subject>Neoplasms, Experimental - genetics</subject><subject>Neoplasms, Experimental - metabolism</subject><subject>Neural Stem Cells - metabolism</subject><subject>Neural Stem Cells - transplantation</subject><subject>Oligonucleotide Array Sequence Analysis</subject><subject>Oncogenes</subject><subject>Oncogenes - genetics</subject><subject>Properties</subject><subject>Reverse Transcriptase Polymerase Chain Reaction</subject><subject>Transfection</subject><subject>Tumor suppressor 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Tanya A</au><au>Neale, Geoffrey</au><au>Olsen, Scott</au><au>Wang, Yong-Dong</au><au>Finkelstein, David</au><au>Wright, Karen</au><au>Gupta, Kirti</au><au>Ellison, David W</au><au>Thomas, Arzu Onar</au><au>Gilbertson, Richard J</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes</atitle><jtitle>Nature genetics</jtitle><stitle>Nat Genet</stitle><addtitle>Nat Genet</addtitle><date>2015-08-01</date><risdate>2015</risdate><volume>47</volume><issue>8</issue><spage>878</spage><epage>887</epage><pages>878-887</pages><issn>1061-4036</issn><eissn>1546-1718</eissn><abstract>Richard Gilbertson and colleagues report an
in vivo
screen of 84 candidate oncogenes and 39 candidate tumor-suppressor genes in ependymoma mouse models. The validated targets are involved in vesicle trafficking, DNA modification and cholesterol biosynthesis.
Cancers are characterized by non-random chromosome copy number alterations that presumably contain oncogenes and tumor-suppressor genes (TSGs). The affected loci are often large, making it difficult to pinpoint which genes are driving the cancer. Here we report a cross-species
in vivo
screen of 84 candidate oncogenes and 39 candidate TSGs, located within 28 recurrent chromosomal alterations in ependymoma. Through a series of mouse models, we validate eight new ependymoma oncogenes and ten new ependymoma TSGs that converge on a small number of cell functions, including vesicle trafficking, DNA modification and cholesterol biosynthesis, identifying these as potential new therapeutic targets.</abstract><cop>New York</cop><pub>Nature Publishing Group US</pub><pmid>26075792</pmid><doi>10.1038/ng.3323</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5329-4968</orcidid><orcidid>https://orcid.org/0000000253294968</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1061-4036 |
| ispartof | Nature genetics, 2015-08, Vol.47 (8), p.878-887 |
| issn | 1061-4036 1546-1718 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4520751 |
| source | MEDLINE; Nature; Alma/SFX Local Collection |
| subjects | 14 14/19 14/34 14/5 45/100 45/22 45/61 59/5 631/114/2785 631/1647/245 631/80 64/60 692/699/67/1922 Agriculture Animal Genetics and Genomics Animals Biomedicine Biosynthesis Cancer Cancer Research Carcinogenesis Cells, Cultured Chromosome Aberrations Chromosomes Copy number variations DNA Copy Number Variations Ependymoma - genetics Ependymoma - metabolism Female Gene Expression Profiling Gene Expression Regulation, Neoplastic Gene Function Genes Genes, Tumor Suppressor Genetic aspects Genetic Predisposition to Disease - genetics HEK293 Cells Human Genetics Humans Identification and classification Kaplan-Meier Estimate Male Mice, Nude Mice, Transgenic Microscopy, Confocal Mutation Neoplasms, Experimental - genetics Neoplasms, Experimental - metabolism Neural Stem Cells - metabolism Neural Stem Cells - transplantation Oligonucleotide Array Sequence Analysis Oncogenes Oncogenes - genetics Properties Reverse Transcriptase Polymerase Chain Reaction Transfection Tumor suppressor genes Tumors |
| title | An in vivo screen identifies ependymoma oncogenes and tumor-suppressor genes |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-24T14%3A27%3A53IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-gale_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=An%20in%20vivo%20screen%20identifies%20ependymoma%20oncogenes%20and%20tumor-suppressor%20genes&rft.jtitle=Nature%20genetics&rft.au=Mohankumar,%20Kumarasamypet%20M&rft.date=2015-08-01&rft.volume=47&rft.issue=8&rft.spage=878&rft.epage=887&rft.pages=878-887&rft.issn=1061-4036&rft.eissn=1546-1718&rft_id=info:doi/10.1038/ng.3323&rft_dat=%3Cgale_pubme%3EA425349491%3C/gale_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1703436980&rft_id=info:pmid/26075792&rft_galeid=A425349491&rfr_iscdi=true |