論文

査読有り
2016年5月

Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults

NATURE GENETICS
  • Takahiko Yasuda
  • ,
  • Shinobu Tsuzuki
  • ,
  • Masahito Kawazu
  • ,
  • Fumihiko Hayakawa
  • ,
  • Shinya Kojima
  • ,
  • Toshihide Ueno
  • ,
  • Naoto Imoto
  • ,
  • Shinji Kohsaka
  • ,
  • Akiko Kunita
  • ,
  • Koichiro Doi
  • ,
  • Toru Sakura
  • ,
  • Toshiaki Yujiri
  • ,
  • Eisei Kondo
  • ,
  • Katsumichi Fujimaki
  • ,
  • Yasunori Ueda
  • ,
  • Yasutaka Aoyama
  • ,
  • Shigeki Ohtake
  • ,
  • Junko Takita
  • ,
  • Eirin Sai
  • ,
  • Masafumi Taniwaki
  • ,
  • Mineo Kurokawa
  • ,
  • Shinichi Morishita
  • ,
  • Masashi Fukayama
  • ,
  • Hitoshi Kiyoi
  • ,
  • Yasushi Miyazaki
  • ,
  • Tomoki Naoe
  • ,
  • Hiroyuki Mano

48
5
開始ページ
569
終了ページ
+
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1038/ng.3535
出版者・発行元
NATURE PUBLISHING GROUP

The oncogenic mechanisms underlying acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; 15-39 years old) remain largely elusive(1-3). Here we have searched for new oncogenes in AYA-ALL by performing RNA-seq analysis of Philadelphia chromosome (Ph)-negative AYA-ALL specimens (n = 73) with the use of a next-generation sequencer. Interestingly, insertion of D4Z4 repeats containing the DUX4 gene into the IGH locus was frequently identified in B cell AYA-ALL, leading to a high level of expression of DUX4 protein with an aberrant C terminus. A transplantation assay in mice demonstrated that expression of DUX4-IGH in pro-B cells was capable of generating B cell leukemia in vivo. DUX4 fusions were preferentially detected in the AYA generation. Our data thus show that DUX4 can become an oncogenic driver as a result of somatic chromosomal rearrangements and that AYA-ALL may be a clinical entity distinct from ALL at other ages.

Web of Science ® 被引用回数 : 93

リンク情報
DOI
https://doi.org/10.1038/ng.3535
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000374834100018&DestApp=WOS_CPL
URL
http://www.scopus.com/inward/record.url?eid=2-s2.0-84961875103&partnerID=MN8TOARS
URL
http://orcid.org/0000-0003-0995-9405

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