Recurrent chimeric fusion RNAs in non-cancer tissues and cells

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dc.contributor.authorBabiceanu, Mihaelaen
dc.contributor.authorQin, Fujunen
dc.contributor.authorXie, Zhongqiuen
dc.contributor.authorJia, Yuemengen
dc.contributor.authorLopez, Kevinen
dc.contributor.authorJanus, Nicken
dc.contributor.authorFacemire, Lorynen
dc.contributor.authorKumar, Shaileshen
dc.contributor.authorPang, Yuweien
dc.contributor.authorQi, Yanjunen
dc.contributor.authorLazar, Iuliana M.en
dc.contributor.authorLi, Huien
dc.contributor.departmentBiological Sciencesen
dc.date.accessioned2019-04-11T18:07:53Zen
dc.date.available2019-04-11T18:07:53Zen
dc.date.issued2016-04-07en
dc.description.abstractGene fusions and their products (RNA and protein) were once thought to be unique features to cancer. However, chimeric RNAs can also be found in normal cells. Here, we performed, curated and analyzed nearly 300 RNA-Seq libraries covering 30 different non-neoplastic human tissues and cells as well as 15 mouse tissues. A large number of fusion transcripts were found. Most fusions were detected only once, while 291 were seen in more than one sample. We focused on the recurrent fusions and performed RNA and protein level validations on a subset. We characterized these fusions based on various features of the fusions, and their parental genes. They tend to be expressed at higher levels relative to their parental genes than the non-recurrent ones. Over half of the recurrent fusions involve neighboring genes transcribing in the same direction. A few sequence motifs were found enriched close to the fusion junction sites. We performed functional analyses on a few widely expressed fusions, and found that silencing them resulted in dramatic reduction in normal cell growth and/or motility. Most chimeras use canonical splicing sites, thus are likely products of 'intergenic splicing'. We also explored the implications of these non-pathological fusions in cancer and in evolution.en
dc.description.notesNCI [CA190713]; American Cancer Society [Research Scholar Grant 126405-RSG-14-065-01-RMC to H.L.]; St. Baldrick's V Scholar. Funding for open access charge: NCI [CA190713].en
dc.description.sponsorshipNCI [CA190713]; American Cancer Society [126405-RSG-14-065-01-RMC]en
dc.format.mimetypeapplication/pdfen
dc.identifier.doihttps://doi.org/10.1093/nar/gkw032en
dc.identifier.eissn1362-4962en
dc.identifier.issn0305-1048en
dc.identifier.issue6en
dc.identifier.pmid26837576en
dc.identifier.urihttp://hdl.handle.net/10919/88890en
dc.identifier.volume44en
dc.language.isoen_USen
dc.rightsCreative Commons Attribution 4.0 Internationalen
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en
dc.subjectprostate-canceren
dc.subjectbreast-canceren
dc.subjectchromosome translocationsen
dc.subjecthuman transcriptomeen
dc.subjectgene fusionsen
dc.subjectseq dataen
dc.subjectlandscapeen
dc.subjectproteinen
dc.subjectidentificationen
dc.subjectindividualsen
dc.titleRecurrent chimeric fusion RNAs in non-cancer tissues and cellsen
dc.title.serialNucleic Acids Researchen
dc.typeArticle - Refereeden
dc.type.dcmitypeTexten

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