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DOI | 10.1126/science.aam8419 |
Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors | |
Anderson, Nathaniel D.1,2; de Borja, Richard1; Young, Matthew D.3; Fuligni, Fabio1; Rosic, Andrej1; Roberts, Nicola D.3; Hajjar, Simon1; Layeghifard, Mehdi1; Novokmet, Ana1; Kowalski, Paul E.1; Anaka, Matthew1; Davidson, Scott4; Zarrei, Mehdi5; Said, Badr Id1; Schreiner, L. Christine1; Marchand, Remi1; Sitter, Joseph1; Gokgoz, Nalan6; Brunga, Ledia1; Graham, Garrett T.7; Fullam, Anthony3; Pillay, Nischalan8,9; Toretsky, Jeffrey A.7; Yoshida, Akihiko10,11; Shibata, Tatsuhiro12,13; Metzler, Markus14; Somers, Gino R.2,15; Scherer, Stephen W.1,5,16,17; Flanagan, Adrienne M.9,10,11; Campbell, Peter J.3,18; Schiffman, Joshua D.19,20; Shago, Mary2,4; Alexandrov, Ludmil B.21,22,23; Wunder, Jay S.24,25; Andrulis, Irene L.6,16; Malkin, David1,26,27; Behjati, Sam3,28; Shlien, Adam1,2,4 | |
2018-08-31 | |
发表期刊 | SCIENCE
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ISSN | 0036-8075 |
EISSN | 1095-9203 |
出版年 | 2018 |
卷号 | 361期号:6405 |
文章类型 | Article |
语种 | 英语 |
国家 | Canada; England; USA; Japan; Germany |
英文摘要 | Sarcomas are cancers of the bone and soft tissue often defined by gene fusions. Ewing sarcoma involves fusions between EWSR1, a gene encoding an RNA binding protein, and E26 transformation-specific (ETS) transcription factors. We explored how and when EWSR1-ETS fusions arise by studying the whole genomes of Ewing sarcomas. In 52 of 124 (42%) of tumors, the fusion gene arises by a sudden burst of complex, loop-like rearrangements, a process called chromoplexy, rather than by simple reciprocal translocations. These loops always contained the disease-defining fusion at the center, but they disrupted multiple additional genes. The loops occurred preferentially in early replicating and transcriptionally active genomic regions. Similar loops forming canonical fusions were found in three other sarcoma types. Chromoplexy-generated fusions appear to be associated with an aggressive form of Ewing sarcoma. These loops arise early, giving rise to both primary and relapse Ewing sarcoma tumors, which can continue to evolve in parallel. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000443547000030 |
WOS关键词 | DIFFERENTIAL EXPRESSION ANALYSIS ; MUTATIONAL PROCESSES ; GENOMIC LANDSCAPE ; EWING SARCOMA ; CANCER ; SIGNATURES ; METASTASIS ; COMPLEXITY ; EVOLUTION ; IMPACT |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/199489 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.Hosp Sick Children, Program Genet & Genome Biol, Toronto, ON, Canada; 2.Univ Toronto, Dept Lab Med & Pathobiol, Toronto, ON, Canada; 3.Wellcome Sanger Inst, Wellcome Genome Campus, Hinxton, Cambs, England; 4.Hosp Sick Children, Dept Paediat Lab Med, Toronto, ON, Canada; 5.Hosp Sick Children, Ctr Appl Genom, Toronto, ON, Canada; 6.Sinai Hlth Syst, Lunenfeld Tanenbaum Res Inst, Toronto, ON, Canada; 7.Georgetown Univ, Dept Oncol & Pediat, Washington, DC USA; 8.UCL, Inst Canc, Huntley St, London, England; 9.Royal Natl Orthopaed Hosp NHS Trust, Histopathol, Stanmore, Middx, England; 10.Natl Canc Ctr, Dept Pathol, Tokyo, Japan; 11.Natl Canc Ctr, Clin Labs, Tokyo, Japan; 12.Natl Canc Ctr, Div Canc Genom, Tokyo, Japan; 13.Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med,Minato Ku, Tokyo, Japan; 14.Univ Hosp Erlangen, Dept Pediat & Adolescent Med, Erlangen, Germany; 15.Univ Toronto, Hosp Sick Children, Dept Pathol, Toronto, ON, Canada; 16.Univ Toronto, Dept Mol Genet, Toronto, ON, Canada; 17.Univ Toronto, McLaughlin Ctr, Toronto, ON, Canada; 18.Univ Cambridge, Dept Haematol, Cambridge, England; 19.Univ Utah, Dept Pediat, Huntsman Canc Inst, Salt Lake City, UT USA; 20.Univ Utah, Dept Oncol Sci, Huntsman Canc Inst, Salt Lake City, UT USA; 21.Univ Calif San Diego, Dept Cellular & Mol Med, La Jolla, CA 92093 USA; 22.Univ Calif San Diego, Dept Bioengn, La Jolla, CA 92093 USA; 23.Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA; 24.Mt Sinai Hosp, Univ Musculoskeletal Oncol Unit, Toronto, ON, Canada; 25.Univ Toronto, Dept Surg, Div Orthopaed Surg, Toronto, ON, Canada; 26.Hosp Sick Children, Div Hematol Oncol, Toronto, ON, Canada; 27.Univ Toronto, Dept Pediat, Toronto, ON, Canada; 28.Univ Cambridge, Dept Paediat, Cambridge, England |
推荐引用方式 GB/T 7714 | Anderson, Nathaniel D.,de Borja, Richard,Young, Matthew D.,et al. Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors[J]. SCIENCE,2018,361(6405). |
APA | Anderson, Nathaniel D..,de Borja, Richard.,Young, Matthew D..,Fuligni, Fabio.,Rosic, Andrej.,...&Shlien, Adam.(2018).Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors.SCIENCE,361(6405). |
MLA | Anderson, Nathaniel D.,et al."Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors".SCIENCE 361.6405(2018). |
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