Journal article
RECURRENT MUTATIONS IN THE U2AF1 SPLICING FACTOR IN MYELODYSPLASTIC SYNDROMES
Nature genetics, Vol.44(1), pp.53-57
01/2012
DOI: 10.1038/ng.1031
PMCID: PMC3247063
PMID: 22158538
Abstract
Myelodysplastic syndromes (MDS) are hematopoietic stem cell disorders that often progress to chemotherapy-resistant secondary acute myeloid leukemia (sAML). We used whole genome sequencing to perform an unbiased comprehensive screen to discover all the somatic mutations in a sAML sample and genotyped these loci in the matched MDS sample. Here we show that a missense mutation affecting the serine at codon 34 (S34) in
U2AF1
was recurrently mutated in 13/150 (8.7%)
de novo
MDS patients, with suggestive evidence of an associated increased risk of progression to sAML. U2AF1 is a U2 auxiliary factor protein that recognizes the AG splice acceptor dinucleotide at the 3′ end of introns and mutations are located in highly conserved zinc fingers in U2AF1
1
,
2
. Mutant U2AF1 promotes enhanced splicing and exon skipping in reporter assays
in vitro
. This novel, recurrent mutation in
U2AF1
implicates altered pre-mRNA splicing as a potential mechanism for MDS pathogenesis.
Details
- Title: Subtitle
- RECURRENT MUTATIONS IN THE U2AF1 SPLICING FACTOR IN MYELODYSPLASTIC SYNDROMES
- Creators
- Timothy A Graubert - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USADong Shen - The Genome Institute, Washington University, St. Louis, MO, USALi Ding - Department of Genetics, Washington University, St. Louis, MO, USATheresa Okeyo-Owuor - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USACara L Lunn - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAJin Shao - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAKilannin Krysiak - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAChristopher C Harris - The Genome Institute, Washington University, St. Louis, MO, USADaniel C Koboldt - The Genome Institute, Washington University, St. Louis, MO, USADavid E Larson - The Genome Institute, Washington University, St. Louis, MO, USAMichael D McLellan - The Genome Institute, Washington University, St. Louis, MO, USADavid J Dooling - The Genome Institute, Washington University, St. Louis, MO, USARachel M Abbott - The Genome Institute, Washington University, St. Louis, MO, USARobert S Fulton - The Genome Institute, Washington University, St. Louis, MO, USAHeather Schmidt - The Genome Institute, Washington University, St. Louis, MO, USAJoelle Kalicki-Veizer - The Genome Institute, Washington University, St. Louis, MO, USAMichelle O’Laughlin - The Genome Institute, Washington University, St. Louis, MO, USAMarcus Grillot - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAJack Baty - Division of Biostatistics, Washington University, St. Louis, MO, USASharon Heath - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAJohn L Frater - Department of Pathology and Immunology, Washington University, St. Louis, MO, USATalat Nasim - Department of Medical and Molecular Genetics, King’s College, Guy’s Hospital, London, UKDaniel C Link - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAMichael H Tomasson - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAPeter Westervelt - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAJohn F DiPersio - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USAElaine R Mardis - Department of Genetics, Washington University, St. Louis, MO, USATimothy J Ley - Department of Internal Medicine, Division of Oncology, Washington University, St. Louis, MO, USARichard K Wilson - Department of Genetics, Washington University, St. Louis, MO, USAMatthew J Walter - Washington University in St. Louis
- Resource Type
- Journal article
- Publication Details
- Nature genetics, Vol.44(1), pp.53-57
- DOI
- 10.1038/ng.1031
- PMID
- 22158538
- PMCID
- PMC3247063
- NLM abbreviation
- Nat Genet
- ISSN
- 1061-4036
- eISSN
- 1546-1718
- Language
- English
- Date published
- 01/2012
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094383702771
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