Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors

Beitrag in einer Fachzeitschrift


Details zur Publikation

Autorinnen und Autoren: Anderson ND, De Borja R, Young MD, Fuligni F, Rosic A, Roberts ND, Hajjar S, Layeghifard M, Novokmet A, Kowalski PE, Anaka M, Davidson S, Zarrei M, Said BI, Schreiner LC, Marchand R, Sitter J, Gokgoz N, Brunga L, Graham GT, Fullam A, Pillay N, Toretsky JA, Yoshida A, Shibata T, Metzler M, Somers GR, Scherer SW, Flanagan AM, Campbell PJ, Schiffman JD, Shago M, Alexandrov LB, Wunder JS, Andrulis IL, Malkin D, Behjati S, Shlien A
Zeitschrift: Science
Jahr der Veröffentlichung: 2018
Band: 361
Heftnummer: 6405
ISSN: 0036-8075
eISSN: 1095-9203


Abstract

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.


FAU-Autorinnen und Autoren / FAU-Herausgeberinnen und Herausgeber

Metzler, Markus PD Dr.
Professur für Kinder- und Jugendmedizin mit dem Schwerpunkt Pädiatrische Onkologie und Hämatologie


Einrichtungen weiterer Autorinnen und Autoren

Georgetown University
Mount Sinai Hospital (MSH)
National Cancer Centre Singapore (NCCS)
Royal National Orthopaedic Hospital Trust
Sinai Health System
The Hospital for Sick Children (SickKids)
University College London (UCL)
University of California, San Diego
University of Toronto
University of Utah
Wellcome Trust Sanger Institute - Genome Research Limited


Zitierweisen

APA:
Anderson, N.D., De Borja, R., Young, M.D., Fuligni, F., Rosic, A., Roberts, N.D.,... Shlien, A. (2018). Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors. Science, 361(6405). https://dx.doi.org/10.1126/science.aam8419

MLA:
Anderson, Nathaniel D., et al. "Rearrangement bursts generate canonical gene fusions in bone and soft tissue tumors." Science 361.6405 (2018).

BibTeX: 

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