High prevalence of MAP2K1 mutations in variant and IGHV4-34-expressing hairy-cell leukemias.
To understand the genetic mechanisms driving variant and IGHV4-34-expressing hairy-cell leukemias, we performed whole-exome sequencing of leukemia samples from ten affected individuals, including six with matched normal samples. We identified activating mutations in the MAP2K1 gene (encoding MEK1) in 5 of these 10 samples and in 10 of 21 samples in a validation set (overall frequency of 15/31), suggesting potential new strategies for treating individuals with these diseases.
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Joshua J
JJ
Waterfall
Laboratory of Molecular Biology, CCR, NCI, US NIH, Bethesda, Maryland, USA.
Evgeny
E
Arons
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Robert L
RL
Walker
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Marbin
M
Pineda
Laboratory of Molecular Biology, CCR, NCI, US NIH, Bethesda, Maryland, USA.
Laura
L
Roth
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
J Keith
JK
Killian
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Ogan D
OD
Abaan
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Sean R
SR
Davis
Laboratory of Molecular Biology, CCR, NCI, US NIH, Bethesda, Maryland, USA.
Robert J
RJ
Kreitman
Genetics Branch, Center for Cancer Research (CCR), National Cancer Institute (NCI), US National Institutes of Health (NIH), Bethesda, Maryland, USA.
Paul S
PS
Meltzer
D064211:Connectin / Q000235:genetics; D004268:DNA-Binding Proteins; D015326:Gene Rearrangement, B-Lymphocyte, Heavy Chain / Q000235:genetics*; D006801:Humans; D007143:Immunoglobulin Heavy Chains / Q000235:genetics*; D007135:Immunoglobulin Variable Region / Q000235:genetics; D007943:Leukemia, Hairy Cell / Q000235:genetics*; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D059645:Mutation Rate; D009687:Nuclear Proteins / Q000235:genetics; D012261:Ribonucleoproteins / Q000235:genetics; D000072668:Splicing Factor U2AF; D014157:Transcription Factors / Q000235:genetics; D016159:Tumor Suppressor Protein p53 / Q000235:genetics
C112476:ARID1A protein, human; D064211:Connectin; D004268:DNA-Binding Proteins; D007143:Immunoglobulin Heavy Chains; D007135:Immunoglobulin Variable Region; D009687:Nuclear Proteins; D012261:Ribonucleoproteins; D000072668:Splicing Factor U2AF; C495901:TP53 protein, human; C577285:TTN protein, human; D014157:Transcription Factors; D016159:Tumor Suppressor Protein p53; C076753:U2AF1 protein, human; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human