Please use this identifier to cite or link to this item: https://doi.org/10.1038/nature10496
Title: Frequent pathway mutations of splicing machinery in myelodysplasia
Authors: Yoshida, K.
Sanada, M.
Shiraishi, Y.
Nowak, D.
Nagata, Y.
Yamamoto, R.
Sato, Y.
Sato-Otsubo, A.
Kon, A.
Nagasaki, M.
Chalkidis, G.
Suzuki, Y.
Shiosaka, M.
Kawahata, R.
Yamaguchi, T.
Otsu, M.
Obara, N.
Sakata-Yanagimoto, M.
Ishiyama, K.
Mori, H.
Nolte, F.
Hofmann, W.-K.
Miyawaki, S.
Sugano, S.
Haferlach, C.
Koeffler, H.P. 
Shih, L.-Y.
Haferlach, T.
Chiba, S.
Nakauchi, H.
Miyano, S.
Ogawa, S.
Issue Date: 6-Oct-2011
Citation: Yoshida, K., Sanada, M., Shiraishi, Y., Nowak, D., Nagata, Y., Yamamoto, R., Sato, Y., Sato-Otsubo, A., Kon, A., Nagasaki, M., Chalkidis, G., Suzuki, Y., Shiosaka, M., Kawahata, R., Yamaguchi, T., Otsu, M., Obara, N., Sakata-Yanagimoto, M., Ishiyama, K., Mori, H., Nolte, F., Hofmann, W.-K., Miyawaki, S., Sugano, S., Haferlach, C., Koeffler, H.P., Shih, L.-Y., Haferlach, T., Chiba, S., Nakauchi, H., Miyano, S., Ogawa, S. (2011-10-06). Frequent pathway mutations of splicing machinery in myelodysplasia. Nature 478 (7367) : 64-69. ScholarBank@NUS Repository. https://doi.org/10.1038/nature10496
Abstract: 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 (∼445 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. © 2011 Macmillan Publishers Limited. All rights reserved.
Source Title: Nature
URI: http://scholarbank.nus.edu.sg/handle/10635/126812
ISSN: 00280836
DOI: 10.1038/nature10496
Appears in Collections:Staff Publications

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