Frequent pathway mutations of splicing machinery in myelodysplasia
書誌事項
- 公開日
- 2011-09-11
- 資源種別
- journal article
- 権利情報
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- http://www.springer.com/tdm
- DOI
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- 10.1038/nature10496
- 公開者
- Springer Science and Business Media LLC
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説明
Myelodysplastic syndromes and related disorders (myelodysplasia) are a heterogeneous group of myeloid neoplasms showing deregulated blood cell production with evidence of myeloid dysplasia and a predisposition to acute myeloid leukaemia, whose pathogenesis is only incompletely understood. Here we report whole-exome sequencing of 29 myelodysplasia specimens, which unexpectedly revealed novel pathway mutations involving multiple components of the RNA splicing machinery, including U2AF35, ZRSR2, SRSF2 and SF3B1. In a large series analysis, these splicing pathway mutations were frequent (∼45 to ∼85%) in, and highly specific to, myeloid neoplasms showing features of myelodysplasia. Conspicuously, most of the mutations, which occurred in a mutually exclusive manner, affected genes involved in the 3'-splice site recognition during pre-mRNA processing, inducing abnormal RNA splicing and compromised haematopoiesis. Our results provide the first evidence indicating that genetic alterations of the major splicing components could be involved in human pathogenesis, also implicating a novel therapeutic possibility for myelodysplasia.
収録刊行物
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- Nature
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Nature 478 (7367), 64-69, 2011-09-11
Springer Science and Business Media LLC
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キーワード
詳細情報 詳細情報について
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- CRID
- 1360565166752066304
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- NII論文ID
- 80021997604
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- ISSN
- 14764687
- 00280836
- https://id.crossref.org/issn/00280836
- https://id.crossref.org/issn/14764687
- http://id.crossref.org/issn/00280836
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- PubMed
- 22064353
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- 資料種別
- journal article
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- データソース種別
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- Crossref
- CiNii Articles
- KAKEN
- OpenAIRE
