气候变化领域集成服务门户(CCPortal): Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia

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DOI	10.1073/pnas.2014967118
	Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia
	Rivera O.D.; Mallory M.J.; Quesnel-Vallières M.; Chatrikhi R.; Schultz D.C.; Carroll M.; Barash Y.; Cherry S.; Lynch K.W.
发表日期	2021
ISSN	00278424
卷号	118 期号:15
英文摘要	Most genes associated with acute myeloid leukemia (AML) are mutated in less than 10% of patients, suggesting that alternative mechanisms of gene disruption contribute to this disease. Here, we find a set of splicing events that alter the expression of a subset of AML-associated genes independent of known somatic mutations. In particular, aberrant splicing triples the number of patients with reduced functional EZH2 compared with that predicted by somatic mutation alone. In addition, we unexpectedly find that the nonsense-mediated decay factor DHX34 exhibits widespread alternative splicing in sporadic AML, resulting in a premature stop codon that phenocopies the loss-of-function germline mutations observed in familial AML. Together, these results demonstrate that classical mutation analysis underestimates the burden of functional gene disruption in AML and highlight the importance of assessing the contribution of alternative splicing to gene dysregulation in human disease. © 2021 National Academy of Sciences. All rights reserved.
英文关键词	Alternative splicing; AML; Cancer; DHX34; EZH2
语种	英语
来源期刊	Proceedings of the National Academy of Sciences of the United States of America
文献类型	期刊论文
条目标识符	http://gcip.llas.ac.cn/handle/2XKMVOVA/179873
作者单位	Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Genetics, University of Pennsylvania, Philadelphia, PA 19104, United States; Graduate Group in Cell and Molecular Biology, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Computer and Information Sciences, School of Engineering, University of Pennsylvania, Philadelphia, PA 19104, United States; Department of Pathology and Laboratory Medicine, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, United States
推荐引用方式 GB/T 7714	Rivera O.D.,Mallory M.J.,Quesnel-Vallières M.,et al. Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia[J],2021,118(15).
APA	Rivera O.D..,Mallory M.J..,Quesnel-Vallières M..,Chatrikhi R..,Schultz D.C..,...&Lynch K.W..(2021).Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia.Proceedings of the National Academy of Sciences of the United States of America,118(15).
MLA	Rivera O.D.,et al."Alternative splicing redefines landscape of commonly mutated genes in acute myeloid leukemia".Proceedings of the National Academy of Sciences of the United States of America 118.15(2021).