Abstract
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.
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Acknowledgements
This work was supported by the Intramural Research Program of the US NIH, NCI, CCR (P.S.M. and R.J.K.) and the Hairy Cell Leukemia Research Foundation (R.J.K.).
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J.J.W., E.A., R.J.K. and P.S.M. conceived the study and supervised analyses. J.J.W. designed and performed analyses. E.A. and R.J.K. provided patient materials. L.R. extracted DNA and processed patient samples. R.L.W. performed exome sequencing. M.P. conducted Sanger sequencing and TaqMan analysis. J.K.K. designed and supervised TaqMan assays. S.R.D. and O.D.A. provided computational scripts. J.J.W., R.J.K. and P.S.M. wrote the manuscript with contributions from all other authors.
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Supplementary Note, Supplementary Tables 1–3 and 5, and Supplementary Figure 1 (PDF 970 kb)
Supplementary Table 4
Candidate driver mutations from whole-exome sequencing (XLS 82 kb)
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Waterfall, J., Arons, E., Walker, R. et al. High prevalence of MAP2K1 mutations in variant and IGHV4-34–expressing hairy-cell leukemias. Nat Genet 46, 8–10 (2014). https://doi.org/10.1038/ng.2828
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DOI: https://doi.org/10.1038/ng.2828
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