Recurrent DUX4 fusions in B cell acute lymphoblastic leukemia of adolescents and young adults
書誌事項
- 公開日
- 2016-03-28
- 資源種別
- journal article
- 権利情報
-
- http://www.springer.com/tdm
- http://www.springer.com/tdm
- DOI
-
- 10.1038/ng.3535
- 公開者
- Springer Science and Business Media LLC
この論文をさがす
説明
The oncogenic mechanisms underlying acute lymphoblastic leukemia (ALL) in adolescents and young adults (AYA; 15-39 years old) remain largely elusive. 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.
収録刊行物
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- Nature Genetics
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Nature Genetics 48 (5), 569-574, 2016-03-28
Springer Science and Business Media LLC
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キーワード
- Adult
- Male
- Adolescent
- Oncogene Proteins, Fusion
- Cohort Studies
- Mice
- Young Adult
- Animals
- Humans
- RNA, Neoplasm
- Child
- Aged
- Aged, 80 and over
- Homeodomain Proteins
- MEF2 Transcription Factors
- Sequence Analysis, RNA
- Age Factors
- Infant, Newborn
- Infant
- Middle Aged
- Precursor Cell Lymphoblastic Leukemia-Lymphoma
- HEK293 Cells
- Child, Preschool
- NIH 3T3 Cells
- Trans-Activators
- Female
- Gene Fusion
- Immunoglobulin Heavy Chains
詳細情報 詳細情報について
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- CRID
- 1360565166759952512
-
- DOI
- 10.1038/ng.3535
-
- ISSN
- 15461718
- 10614036
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- PubMed
- 27898077
-
- 資料種別
- journal article
-
- データソース種別
-
- Crossref
- KAKEN
- OpenAIRE
