Frequent pathway mutations of splicing machinery in myelodysplasia
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 (∼45 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.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In myelodysplastic syndromes, mutations in several components of the core splicing apparatus cause very specific splicing defects in particular transcripts and lead to a highly tissue-specific phenotype.
“mutations in several components of the core splicing apparatus, such as U2 small nuclear ribonucleoprotein auxiliary factor 2 (U2AF65), splicing factor 3B, subunit 1 (SF3B1) and other proteins, were found to cause very specific splicing defects in particular transcripts and to lead to a highly tissue-specific phenotype185–187.”
From The neurogenetics of alternative splicing (2016) · cites this paper as [185]
Cites
Subramanian, A., Tamayo, P., Mootha, V. K., Mukherjee, S., Ebert, B. L., Gillette, M. A., Paulovich, A., Pomeroy, S. L., Golub, T. R., Lander, E. S., et al. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0506580102 · Cited by 53,625 · see citing works
Sequencing technologies – the next generation
Metzker, M. L. (2010) · Nature Reviews Genetics · doi:10.1038/nrg2626 · Cited by 7,066 · see citing works
Next-generation DNA sequencing
Shendure, J., & Ji, H. (2008) · Nature Biotechnology · doi:10.1038/nbt1486 · Cited by 4,509 · see citing works
The Spliceosome: Design Principles of a Dynamic RNP Machine
Wahl, M. C., Will, C. L., & Lührmann, R. (2009) · Cell · doi:10.1016/j.cell.2009.02.009 · Cited by 2,665 · see citing works
Recurring mutations found by sequencing an acute myeloid leukemia genome
Mardis, E. R., Ding, L., Dooling, D. J., Larson, D. E., McLellan, M. D., Chen, K., Koboldt, D. C., Fulton, R. S., Delehaunty, K. D., McGrath, S. D., et al. (2009) · New England Journal of Medicine · doi:10.1056/nejmoa0903840 · Cited by 2,219 · see citing works
<i>DNMT3A</i> Mutations in Acute Myeloid Leukemia
Ley, T. J., Ding, L., Walter, M. J., McLellan, M. D., Lamprecht, T., Larson, D. E., Kandoth, C., Payton, J. E., Baty, J., Welch, J., et al. (2010) · New England Journal of Medicine · doi:10.1056/nejmoa1005143 · Cited by 1,983 · see citing works
Morin, R. D., Johnson, N. A., Severson, T., Mungall, A. J. J., An, J., Goya, R., Paul, J. E., Boyle, M., Woolcock, B. W., Kuchenbauer, F. C., et al. (2010) · Nature Genetics · doi:10.1038/ng.518 · Cited by 1,670 · see citing works
Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
Puente, X. S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G. R., Villamor, N., Escaramís, G., Jares, P., Beà, S., González, M., et al. (2011) · Nature · doi:10.1038/nature10113 · Cited by 1,512 · see citing works
Initial genome sequencing and analysis of multiple myeloma
Chapman, M. A., Lawrence, M. S., Keats, J. J., Cibulskis, K., Sougnez, C. L., Schinzel, A. C., Harview, C. L., Brunet, J.-P., Ahmann, G. J., Adli, M., et al. (2011) · Nature · doi:10.1038/nature09837 · Cited by 1,422 · see citing works
DNA sequencing of a cytogenetically normal acute myeloid leukaemia genome
Ley, T. J., Mardis, E. R., Ding, L., Fulton, B., McLellan, M. D., Chen, K., Dooling, D. J., Dunford-Shore, B. H., McGrath, S. D., Hickenbotham, M. T., et al. (2008) · Nature · doi:10.1038/nature07485 · Cited by 1,415 · see citing works
Mechanisms of alternative splicing regulation: insights from molecular and genomics approaches
Chen, M., & Manley, J. L. (2009) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm2777 · Cited by 1,284 · see citing works
Exome sequencing identifies frequent mutation of the SWI/SNF complex gene PBRM1 in renal carcinoma
Varela, I., Tarpey, P. S., Raine, K. M., Huang, D., Ong, C. K., Stephens, P., Davies, H. R., Jones, D., Lin, M., Teague, J. W., et al. (2011) · Nature · doi:10.1038/nature09639 · Cited by 1,278 · see citing works
Nonsense-mediated mRNA decay: splicing, translation and mRNP dynamics
Maquat, L. E. (2004) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm1310 · Cited by 1,214 · see citing works
Mutational evolution in a lobular breast tumour profiled at single nucleotide resolution
Shah, S. P., Morin, R. D., Khattra, J. S., Prentice, L., Pugh, T. J., Burleigh, A., Delaney, A. D., Gelmon, K. A., Guliany, R., Senz, J., et al. (2009) · Nature · doi:10.1038/nature08489 · Cited by 1,063 · see citing works
Identification of RPS14 as a 5q- syndrome gene by RNA interference screen
Ebert, B. L., Pretz, J. L., Bosco, J., Chang, C. Y., Tamayo, P., Galili, N., Raza, A., Root, D. E., Attar, E. C., Ellis, S. R., et al. (2008) · Nature · doi:10.1038/nature06494 · Cited by 925 · see citing works
Alternative pre-mRNA splicing regulation in cancer: pathways and programs unhingedPreprint
David, C. J., & Manley, J. L. (2010) · Genes & Development · doi:10.1101/gad.1973010 · Cited by 815 · see citing works
Campbell, P. J., Stephens, P. J., Pleasance, E., O’Meara, S., Li, H., Santarius, T., Stebbings, L. A., Leroy, C., Edkins, S., Hardy, C. W., et al. (2008) · Nature Genetics · doi:10.1038/ng.128 · Cited by 812 · see citing works
Yan, X., Xu, J., Gu, Z., Pan, C., Lü, G., Shen, Y., Shi, J., Zhu, Y., Tang, L., Zhang, X., et al. (2011) · Nature Genetics · doi:10.1038/ng.788 · Cited by 806 · see citing works
Haase, D. T., Germing, U., Schanz, J., Pfeilstöcker, M., Nösslinger, T., Hildebrandt, B., Kündgen, A., Lübbert, M., Kunzmann, R., Giagounidis, A. A. N., et al. (2007) · Blood · doi:10.1182/blood-2007-03-082404 · Cited by 792 · see citing works
Nannya, Y., Sanada, M., Nakazaki, K., Hosoya, N., Wang, L., Hangaishi, A., Kurokawa, M., Chiba, S., Bailey, D. K., Kennedy, G. C., et al. (2005) · Cancer Research · doi:10.1158/0008-5472.can-05-0465 · Cited by 639 · see citing works
Self-citationNi, J. Z., Grate, L. R., Donohue, J. P., Preston, C. G., Nobida, N., O’Brien, G. S., Shiue, L., Clark, T. A., Blume, J. E., & Ares, M. (2007) · Genes & Development · doi:10.1101/gad.1525507 · Cited by 551 · see citing works
Ma, X., Does, M. B., Raza, A., & Mayne, S. T. (2007) · Cancer · doi:10.1002/cncr.22570 · Cited by 537 · see citing works
The mutation spectrum revealed by paired genome sequences from a lung cancer patient
Lee, W., Jiang, Z., Liu, J., Haverty, P. M., Guan, Y., Stinson, J., Yue, P., Zhang, Y., Pant, K. P., Bhatt, D., et al. (2010) · Nature · doi:10.1038/nature09004 · Cited by 486 · see citing works
Gain-of-function of mutated C-CBL tumour suppressor in myeloid neoplasms
Sanada, M., Suzuki, T., Shih, L., Otsu, M., Kato, M., Yamazaki, S., Tamura, A., Honda, H., Sakata‐Yanagimoto, M., Kumano, K., et al. (2009) · Nature · doi:10.1038/nature08240 · Cited by 401 · see citing works
Self-citationCalvo, S. E., Tucker, E. J., Compton, A. G., Kirby, D. M., Crawford, G., Burtt, N. P., Rivas, M. A., Guiducci, C., Bruno, D. L., Goldberger, O., et al. (2010) · Nature Genetics · doi:10.1038/ng.659 · Cited by 362 · see citing works
Myelodysplastic syndromes: the complexity of stem-cell diseases
Corey, S. J., Minden, M. D., Barber, D. L., Kantarjian, H. M., Wang, J. C. Y., & Schimmer, A. D. (2007) · Nature reviews. Cancer · doi:10.1038/nrc2047 · Cited by 341 · see citing works
A p53-dependent mechanism underlies macrocytic anemia in a mouse model of human 5q– syndrome
Barlow, J. L., Drynan, L. F., Hewett, D. R., Holmes, L. R., Lorenzo-Abalde, S., Lane, A. L., Jolin, H. E., Pannell, R., Middleton, A. J., Wong, S. H., et al. (2009) · Nature Medicine · doi:10.1038/nm.2063 · Cited by 337 · see citing works
A POPULATION-SPECIFIC HTR2B STOP CODON PREDISPOSES TO SEVERE IMPULSIVITY
Bevilacqua, L., Doly, S., Kaprio, J., Yuan, Q., Tikkanen, R., Paunio, T., Zhou, Z.-F., Wedenoja, J., Maroteaux, L., Diaz, S., et al. (2010) · Nature · doi:10.1038/nature09629 · Cited by 321 · see citing works
Unraveling the Molecular Pathophysiology of Myelodysplastic Syndromes
Bejar, R. L., Levine, R. L., & Ebert, B. L. (2011) · Journal of Clinical Oncology · doi:10.1200/jco.2010.31.1175 · Cited by 303 · see citing works
He, H., Liyanarachchi, S., Akagi, K., Nagy, R. S., Li, J., Dietrich, R. C., Li, W., Sebastian, N., Wen, B., Xin, B., et al. (2011) · Science · doi:10.1126/science.1200587 · Cited by 262 · see citing works
Alternative splicing: an emerging topic in molecular and clinical oncology
Pajares, M. J., Ezponda, T., Catena, R., Calvo, A., Pı́o, R., & Montuenga, L. M. (2007) · The Lancet Oncology · doi:10.1016/s1470-2045(07)70104-3 · Cited by 261 · see citing works
Yamamoto, G., Nannya, Y., Kato, M., Sanada, M., Levine, R. L., Kawamata, N., Hangaishi, A., Kurokawa, M., Chiba, S., Gilliland, D. G., et al. (2007) · The American Journal of Human Genetics · doi:10.1086/518809 · Cited by 242 · see citing works
Self-citationAssociation of TALS Developmental Disorder with Defect in Minor Splicing Component U4atac snRNA
Edery, P., Marcaillou, C., Sahbatou, M., Labalme, A., Chastang, J., Touraine, R. L., Tubacher, E., Senni, F., Bober, M. B., Nampoothiri, S., et al. (2011) · Science · doi:10.1126/science.1202205 · Cited by 228 · see citing works
Adult mouse hematopoietic stem cells: purification and single-cell assays
Ema, H., Morita, Y., Yamazaki, S., Matsubara, A., Seita, J., Tadokoro, Y., Kondo, H., Takano, H., & Nakauchi, H. (2006) · Nature Protocols · doi:10.1038/nprot.2006.447 · Cited by 184 · see citing works
Self-citationXiao, R., Sun, Y., Ding, J., Lin, S., Rose, D. W., Rosenfeld, M. G., Fu, X., & Li, X. (2007) · Molecular and Cellular Biology · doi:10.1128/mcb.00288-07 · Cited by 159 · see citing works
Tronchre, H., Wang, J., & Fu, X. (1997) · Nature · doi:10.1038/41137 · Cited by 109 · see citing works
Shen, H., Zheng, X., Luecke, S., & Green, M. R. (2010) · Genes & Development · doi:10.1101/gad.1974810 · Cited by 97 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
Vogelstein, B., Papadopoulos, N., Velculescu, V. E., Zhou, S., Diaz, L. A., & Kinzler, K. W. (2013) · Science · doi:10.1126/science.1235122 · Cited by 7,863 · see citing works
U1 snRNP regulates cancer cell migration and invasion in vitro
Oh, J.-M., Venters, C. C., Di, C., Pinto, A. M., Wan, L., Younis, I., Cai, Z., Arai, C., So, B. R., Duan, J., et al. (2020) · Nature Communications · doi:10.1038/s41467-019-13993-7 · Cited by 7,157 · see citing works
Predicting splicing from primary sequence with deep learning
Jaganathan, K., Kyriazopoulou Panagiotopoulou, S., McRae, J. F., Darbandi, S. F., Knowles, D., Li, Y. I., Kosmicki, J. A., Arbelaez, J., Cui, W., Schwartz, G. B., et al. (2019) · Cell · doi:10.1016/j.cell.2018.12.015 · Cited by 2,853 · see citing works
Standards and Guidelines for the Interpretation and Reporting of Sequence Variants in Cancer
Li, M. M., Datto, M., Duncavage, E. J., Kulkarni, S., Lindeman, N. I., Roy, S., Tsimberidou, A. M., Vnencak‐Jones, C. L., Wolff, D. J., Younes, A., et al. (2016) · Journal of Molecular Diagnostics · doi:10.1016/j.jmoldx.2016.10.002 · Cited by 2,054 · see citing works
Age-related mutations associated with clonal hematopoietic expansion and malignancies
Xie, M., Lu, C., Wang, J., McLellan, M. D., Johnson, K. J., Wendl, M. C., McMichael, J. F., Schmidt, H. K., Yellapantula, V., Miller, C. A., et al. (2014) · Nature Medicine · doi:10.1038/nm.3733 · Cited by 1,874 · see citing works
Clinical and biological implications of driver mutations in myelodysplastic syndromes
Papaemmanuil, E., Gerstung, M., Malcovati, L., Tauro, S., Gundem, G., Van Loo, P., Yoon, C. J., Ellis, P., Wedge, D. C., Pellagatti, A., et al. (2013) · Blood · doi:10.1182/blood-2013-08-518886 · Cited by 1,832 · see citing works
Mapping the Hallmarks of Lung Adenocarcinoma with Massively Parallel Sequencing
Imielinski, M., Berger, A. H., Hammerman, P. S., Hernandez, B., Pugh, T. J., Hodis, E., Cho, J., Suh, J., Capelletti, M., Sivachenko, A., et al. (2012) · Cell · doi:10.1016/j.cell.2012.08.029 · Cited by 1,789 · see citing works
Landscape of genetic lesions in 944 patients with myelodysplastic syndromes
Haferlach, T., Nagata, Y., Grossmann, V, Okuno, Y., Bacher, U., Nagae, G., Schnittger, S., Sanada, M., Kon, A., Alpermann, T., et al. (2014) · Leukemia · doi:10.1038/leu.2013.336 · Cited by 1,532 · see citing works
Self-citationEvolution and impact of subclonal mutations in chronic lymphocytic leukemia
Landau, D. A., Carter, S. L., Stojanov, P., McKenna, A., Stevenson, K., Lawrence, M. S., Sougnez, C., Stewart, C., Sivachenko, A., Wang, L., et al. (2013) · Cell · doi:10.1016/j.cell.2013.01.019 · Cited by 1,379 · see citing works
Lessons from the Cancer Genome
Garraway, L. A., & Lander, E. S. (2013) · Cell · doi:10.1016/j.cell.2013.03.002 · Cited by 1,322 · see citing works
Sotillo, E., Barrett, D. M., Black, K. L., Bagashev, A., Oldridge, D. A., Wu, G. S., Sussman, R. T., Lanauze, C. B., Ruella, M., Gazzara, M. R., et al. (2015) · Cancer Discovery · doi:10.1158/2159-8290.cd-15-1020 · Cited by 1,251 · see citing works
Integrated molecular analysis of clear-cell renal cell carcinoma
Sato, Y., Yoshizato, T., Shiraishi, Y., Maekawa, S., Okuno, Y., Kamura, T., Shimamura, T., Sato‐Otsubo, A., Nagae, G., Suzuki, H., et al. (2013) · Nature Genetics · doi:10.1038/ng.2699 · Cited by 1,223 · see citing works
Self-citationScotti, M. M., & Swanson, M. S. (2015) · Nature Reviews Genetics · doi:10.1038/nrg.2015.3 · Cited by 1,130 · see citing works
A day in the life of the spliceosome
Matera, A. G., & Wang, Z. (2014) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3742 · Cited by 1,074 · see citing works
Goodall, G. J., & Wickramasinghe, V. O. (2020) · Nature reviews. Cancer · doi:10.1038/s41568-020-00306-0 · Cited by 1,070 · see citing works
Context-dependent control of alternative splicing by RNA-binding proteins
Fu, X.-D., & Ares, M. (2014) · Nature Reviews Genetics · doi:10.1038/nrg3778 · Cited by 1,044 · see citing works
Quesada, V., Conde, L., Villamor, N., Ordóñez, G. R., Jares, P., Bassaganyas, L., Ramsay, A. J., Beà, S., Pinyol, M., Martínez‐Trillos, A., et al. (2011) · Nature Genetics · doi:10.1038/ng.1032 · Cited by 987 · see citing works
Mutational landscape and clonal architecture in grade II and III gliomas
Suzuki, H., Aoki, K., Chiba, K., Sato, Y., Shiozawa, Y., Shiraishi, Y., Shimamura, T., Niida, A., Motomura, K., Ohka, F., et al. (2015) · Nature Genetics · doi:10.1038/ng.3273 · Cited by 831 · see citing works
Self-citationIntegrated molecular analysis of adult T cell leukemia/lymphoma
Kataoka, K., Nagata, Y., Kitanaka, A., Shiraishi, Y., Shimamura, T., Yasunaga, J., Totoki, Y., Chiba, K., Sato‐Otsubo, A., Nagae, G., et al. (2015) · Nature Genetics · doi:10.1038/ng.3415 · Cited by 819 · see citing works
Self-citationExploiting the Mutanome for Tumor Vaccination
Castle, J. C., Kreiter, S., Diekmann, J., Löwer, M., van de Roemer, N., de Graaf, J., Selmi, A., Diken, M., Boegel, S., Paret, C., et al. (2012) · Cancer Research · doi:10.1158/0008-5472.can-11-3722 · Cited by 802 · see citing works
Mutations and prognosis in primary myelofibrosis
Vannucchi, A. M., Lasho, T. L., Guglielmelli, P., Biamonte, F., Pardanani, A. D., Pereira, A., Finke, C. M., Score, J., Gangat, N., Mannarelli, C., et al. (2013) · Leukemia · doi:10.1038/leu.2013.119 · Cited by 770 · see citing works
Roles and mechanisms of alternative splicing in cancer — implications for care
Bonnal, S., López‐Oreja, I., & Valcárcel, J. (2020) · Nature Reviews Clinical Oncology · doi:10.1038/s41571-020-0350-x · Cited by 741 · see citing works
RNA splicing factors as oncoproteins and tumour suppressors
Dvinge, H., Kim, E. H., Abdel-Wahab, O. I., & Bradley, R. K. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.51 · Cited by 684 · see citing works
The genetics of myelodysplastic syndrome: from clonal haematopoiesis to secondary leukaemia
Sperling, A. S., Gibson, C. J., & Ebert, B. L. (2016) · Nature reviews. Cancer · doi:10.1038/nrc.2016.112 · Cited by 676 · see citing works
Genetic basis and molecular pathophysiology of classical myeloproliferative neoplasms
Vainchenker, W., & Královics, R. (2016) · Blood · doi:10.1182/blood-2016-10-695940 · Cited by 673 · see citing works
Mechanisms and function of substrate recruitment by F-box proteins
Skaar, J. R., Pagan, J. K., & Pagano, M. (2013) · Nature Reviews Molecular Cell Biology · doi:10.1038/nrm3582 · Cited by 671 · see citing works
Malcovati, L., Hellström‐Lindberg, E., Bowen, D., Adès, L., Čermák, J., del Cañizo, C., Porta, M. G. D., Fenaux, P., Gattermann, N., Germing, U., et al. (2013) · Blood · doi:10.1182/blood-2013-03-492884 · Cited by 667 · see citing works
Somatic RHOA mutation in angioimmunoblastic T cell lymphoma
Sakata‐Yanagimoto, M., Enami, T., Yoshida, K., Shiraishi, Y., Ishii, R., Miyake, Y., Muto, H., Tsuyama, N., Sato‐Otsubo, A., Okuno, Y., et al. (2014) · Nature Genetics · doi:10.1038/ng.2872 · Cited by 649 · see citing works
Self-citationSomatic Mutations and Clonal Hematopoiesis in Aplastic Anemia
Yoshizato, T., Dumitriu, B., Hosokawa, K., Makishima, H., Yoshida, K., Townsley, D., Sato-Otsubo, A., Sato, Y., Liu, D., Suzuki, H., et al. (2015) · New England Journal of Medicine · doi:10.1056/nejmoa1414799 · Cited by 646 · see citing works
Self-citationAge-related remodelling of oesophageal epithelia by mutated cancer drivers
Yokoyama, A., Kakiuchi, N., Yoshizato, T., Nannya, Y., Suzuki, H., Takeuchi, Y., Shiozawa, Y., Sato, Y., Aoki, K., Kim, S. K., et al. (2019) · Nature · doi:10.1038/s41586-018-0811-x · Cited by 628 · see citing works
Self-citationGenomic and molecular characterization of esophageal squamous cell carcinoma
Lin, D., Hao, J., Nagata, Y., Xu, L., Li, S., Meng, X., Sato, Y., Okuno, Y., Varela, A. M., Ding, L., et al. (2014) · Nature Genetics · doi:10.1038/ng.2935 · Cited by 622 · see citing works
Self-citationRecurrent mutations in the U2AF1 splicing factor in myelodysplastic syndromes
Graubert, T. A., Shen, D., Ding, L., Okeyo-Owuor, T., Shirai, C. L., Shao, J., Krysiak, K., Harris, C. C., Koboldt, D. C., Larson, D. E., et al. (2011) · Nature Genetics · doi:10.1038/ng.1031 · Cited by 582 · see citing works
Targeted Disruption of HLA Genes via CRISPR-Cas9 Generates iPSCs with Enhanced Immune Compatibility
Xu, H., Wang, B., Ono, M., Kagita, A., Fujii, K., Sasakawa, N., Ueda, T., Gee, P., Nishikawa, M., Nomura, M., et al. (2019) · Cell stem cell · doi:10.1016/j.stem.2019.02.005 · Cited by 581 · see citing works
RNA splicing dysregulation and the hallmarks of cancer
Bradley, R. K., & Anczuków, O. (2023) · Nature Reviews Cancer · doi:10.1038/s41568-022-00541-7 · Cited by 579 · see citing works
The Spectrum of SWI/SNF Mutations, Ubiquitous in Human Cancers
Shain, A. H., & Pollack, J. R. (2013) · PLoS ONE · doi:10.1371/journal.pone.0055119 · Cited by 578 · see citing works
SRSF2 Mutations Contribute to Myelodysplasia by Mutant-Specific Effects on Exon Recognition
Kim, E., Ilagan, J. O., Liang, Y., Daubner, G. M., Lee, S. C.-W., Ramakrishnan, A., Li, Y., Chung, Y. R., Micol, J.-B., Murphy, M. E., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.04.006 · Cited by 575 · see citing works
Cervical cancer in low and middle‑income countries (Review)
Hull, R., Mbele, M., Makhafola, T. J., Hicks, C., Wang, S., Reis, R. M., Mehrotra, R., Mkhize‐Kwitshana, Z. L., Kibiki, G. S., Bates, D. O., et al. (2020) · Oncology Letters · doi:10.3892/ol.2020.11754 · Cited by 570 · see citing works
Epigenomic analysis detects widespread gene-body DNA hypomethylation in chronic lymphocytic leukemia
Kulis, M., Heath, S. C., Bibikova, M. V., Queirós, A. C., Navarro, A., Clot, G., Martínez‐Trillos, A., Castellano, G., Heath, I. B., Pinyol, M., et al. (2012) · Nature Genetics · doi:10.1038/ng.2443 · Cited by 568 · see citing works
TET2 mutations predict response to hypomethylating agents in myelodysplastic syndrome patients
Bejar, R. L., Lord, A. M., Stevenson, K. E., Bar‐Natan, M., Pérez-Ladaga, A., Zaneveld, J. E., Wang, H., Caughey, B. A., Stojanov, P., Getz, G. A., et al. (2014) · Blood · doi:10.1182/blood-2014-06-582809 · Cited by 563 · see citing works
Therapeutic targeting of splicing in cancer
Lee, S. C.-W., & Abdel-Wahab, O. I. (2016) · Nature Medicine · doi:10.1038/nm.4165 · Cited by 556 · see citing works
Prognostic Score Including Gene Mutations in Chronic Myelomonocytic Leukemia
Itzykson, R., Kosmider, O., Renneville, A., Gelsi‐Boyer, V., Meggendorfer, M., Morabito, M., Berthon, C., Adès, L., Fenaux, P., Beyne‐Rauzy, O., et al. (2013) · Journal of Clinical Oncology · doi:10.1200/jco.2012.47.3314 · Cited by 546 · see citing works
Self-citationGenomics of Acute Myeloid Leukemia Diagnosis and Pathways
Bullinger, L., Döhner, K., & Döhner, H. (2017) · Journal of Clinical Oncology · doi:10.1200/jco.2016.71.2208 · Cited by 544 · see citing works
Martin, M., Maßhöfer, L., Ketteler, P., Rahmann, S., Metz, C. H. D., Bornfeld, N., van de Nes, J. A. P., Klein‐Hitpaß, L., Hinnebusch, A. G., Horsthemke, B., et al. (2013) · Nature Genetics · doi:10.1038/ng.2674 · Cited by 536 · see citing works
JAK/STAT signaling in hematological malignancies
Vainchenker, W., & Constantinescu, S. N. (2013) · Oncogene · doi:10.1038/onc.2012.347 · Cited by 528 · see citing works
Seiler, M., Yoshimi, A., Darman, R. B., Chan, B., Keaney, G. F., Thomas, M., Agrawal, A. A., Caleb, B. L., Csibi, A., Sean, E. E., et al. (2018) · Nature Medicine · doi:10.1038/nm.4493 · Cited by 513 · see citing works
DNMT3A in haematological malignancies
Yang, L., Rau, R. E., & Goodell, M. A. (2015) · Nature reviews. Cancer · doi:10.1038/nrc3895 · Cited by 509 · see citing works
Malcovati, L., Papaemmanuil, E., Bowen, D., Boultwood, J., Porta, M. G. D., Pascutto, C., Travaglino, E., Groves, M. J., Godfrey, A. L., Ambaglio, I., et al. (2011) · Blood · doi:10.1182/blood-2011-09-377275 · Cited by 496 · see citing works
Cazzola, M. (2020) · New England Journal of Medicine · doi:10.1056/nejmra1904794 · Cited by 496 · see citing works
Nuclear speckles: molecular organization, biological function and role in disease
Gałgański, Ł., Urbanek-Trzeciak, M. O., & Krzyżosiak, W. J. (2017) · Nucleic Acids Research · doi:10.1093/nar/gkx759 · Cited by 489 · see citing works
Emerging patterns of somatic mutations in cancer
Watson, I. R., Takahashi, K., Futreal, P. A., & Chin, L. (2013) · Nature Reviews Genetics · doi:10.1038/nrg3539 · Cited by 481 · see citing works
Clinical significance of somatic mutation in unexplained blood cytopenia
Malcovati, L., Gallì, A., Travaglino, E., Ambaglio, I., Rizzo, E., Molteni, E., Elena, C., Ferretti, V. V., Catricalà, S., Bono, E. B., et al. (2017) · Blood · doi:10.1182/blood-2017-01-763425 · Cited by 476 · see citing works
Self-citationRegulation of splicing by SR proteins and SR protein-specific kinases
Zhou, Z., & Fu, X. (2013) · Chromosoma · doi:10.1007/s00412-013-0407-z · Cited by 471 · see citing works
Aberrant RNA splicing in cancer; expression changes and driver mutations of splicing factor genes
Sveen, A., Kilpinen, S. K., Ruusulehto, A., Lothe, R. A., & Skotheim, R. I. (2015) · Oncogene · doi:10.1038/onc.2015.318 · Cited by 463 · see citing works
Tumor-suppressor genes that escape from X-inactivation contribute to cancer sex bias
Dunford, A. J., Weinstock, D. M., Savova, V., Schumacher, S. E., Cleary, J. P., Yoda, A., Sullivan, T. J., Hess, J. M., Gimelbrant, A. A., Beroukhim, R., et al. (2016) · Nature Genetics · doi:10.1038/ng.3726 · Cited by 459 · see citing works
Pre-mRNA splicing in disease and therapeutics
Singh, R. K., & Cooper, T. A. (2012) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2012.06.006 · Cited by 456 · see citing works
Darman, R. B., Seiler, M., Agrawal, A. A., Lim, K., Peng, S., Aird, D. R., Bailey, S., Bhavsar, E. B., Chan, B., Colla, S., et al. (2015) · Cell Reports · doi:10.1016/j.celrep.2015.09.053 · Cited by 455 · see citing works
Molecular landscape of acute myeloid leukemia in younger adults and its clinical relevance
Grimwade, D. J., Ivey, A., & Huntly, B. J. P. (2015) · Blood · doi:10.1182/blood-2015-07-604496 · Cited by 451 · see citing works
Crystal Structure of TET2-DNA Complex: Insight into TET-Mediated 5mC Oxidation
Hu, L., Li, Z., Cheng, J., Rao, Q., Gong, W., Liu, M., Shi, Y. G., Zhu, J., Wang, P., & Xu, Y. (2013) · Cell · doi:10.1016/j.cell.2013.11.020 · Cited by 448 · see citing works
Bejar, R. L., Stevenson, K. E., Caughey, B. A., Abdel-Wahab, O. I., Steensma, D. P., Galili, N., Raza, A., Kantarjian, H. M., Levine, R. L., Neuberg, D. S., et al. (2012) · Journal of Clinical Oncology · doi:10.1200/jco.2011.40.7379 · Cited by 442 · see citing works
Seiler, M., Peng, S., Agrawal, A. A., Palacino, J. J., Teng, T., Zhu, P., Smith, P. G., Johnson, R., Demchok, J. A., Felau, I., et al. (2018) · Cell Reports · doi:10.1016/j.celrep.2018.01.088 · Cited by 438 · see citing works
Inherited and Somatic Defects in DDX41 in Myeloid Neoplasms
Polprasert, C., Schulze, I., Sekeres, M. A., Makishima, H., Przychodzen, B. P., Hosono, N., Singh, J., Padgett, R. A., Gu, X., Phillips, J. G., et al. (2015) · Cancer Cell · doi:10.1016/j.ccell.2015.03.017 · Cited by 435 · see citing works
Self-citationLiang, D., Tatomer, D. C., Luo, Z., Wu, H., Yang, L. C., Chen, L., Cherry, S. R., & Wilusz, J. E. (2017) · Molecular Cell · doi:10.1016/j.molcel.2017.10.034 · Cited by 435 · see citing works
SF3B1 mutation identifies a distinct subset of myelodysplastic syndrome with ring sideroblasts
Malcovati, L., Karimi, M., Papaemmanuil, E., Ambaglio, I., Jädersten, M., Jansson, M., Elena, C., Gallì, A., Walldin, G., Della Porta, M. G., et al. (2015) · Blood · doi:10.1182/blood-2015-03-633537 · Cited by 434 · see citing works
Landscape Of Genetic Lesions In 944 Patients With Myelodysplastic Syndromes
Nagata, Y., Grossmann, V., Okuno, Y., Bacher, U., Nagae, G., Schnittger, S., Shiozawa, Y., Kon, A., Alpermann, T., Yoshida, K., et al. (2013) · Blood · doi:10.1182/blood.v122.21.521.521 · Cited by 430 · see citing works
Self-citationKeersmaecker, K. D., Atak, Z. K., Li, N., Vicente, C., Patchett, S., Girardi, T., Gianfelici, V., Geerdens, E., Clappier, E., Porcu, M., et al. (2012) · Nature Genetics · doi:10.1038/ng.2508 · Cited by 426 · see citing works
Thol, F. R., Kade, S., Schlarmann, C., Löffeld, P., Morgan, M. A., Krauter, J., Włodarski, M. W., Kölking, B., Wichmann, M., Görlich, K., et al. (2012) · Blood · doi:10.1182/blood-2011-12-399337 · Cited by 420 · see citing works
Self-citationDynamics of clonal evolution in myelodysplastic syndromes
Makishima, H., Yoshizato, T., Yoshida, K., Sekeres, M. A., Radivoyevitch, T., Suzuki, H., Przychodzen, B. P., Nagata, Y., Meggendorfer, M., Sanada, M., et al. (2016) · Nature Genetics · doi:10.1038/ng.3742 · Cited by 420 · see citing works
Self-citationThe spliceosome as a target of novel antitumour drugs
Bonnal, S., Vigevani, L., & Valcárcel, J. (2012) · Nature Reviews Drug Discovery · doi:10.1038/nrd3823 · Cited by 403 · see citing works
Perspective on Oncogenic Processes at the End of the Beginning of Cancer Genomics
Ding, L., Bailey, M. H., Porta-Pardo, E., Thorsson, V., Colaprico, A., Bertrand, D., Gibbs, D. L., Weerasinghe, A., Huang, K.-L., Tokheim, C., et al. (2018) · Cell · doi:10.1016/j.cell.2018.03.033 · Cited by 399 · see citing works
Bejar, R. L., Stevenson, K. E., Caughey, B. A., Lindsley, R. C., Mar, B. G., Stojanov, P., Getz, G. A., Steensma, D. P., Ritz, J., Soiffer, R. J., et al. (2014) · Journal of Clinical Oncology · doi:10.1200/jco.2013.52.3381 · Cited by 396 · see citing works
Adès, L., Itzykson, R., & Fenaux, P. (2014) · The Lancet · doi:10.1016/s0140-6736(13)61901-7 · Cited by 396 · see citing works
Alsafadi, S., Houy, A., Battistella, A., Popova, T. G., Wassef, M. A., Henry, E., Tirode, F., Constantinou, A., Piperno-Neumann, S., Roman‐Roman, S., et al. (2016) · Nature Communications · doi:10.1038/ncomms10615 · Cited by 385 · see citing works
Recurrent mutations in multiple components of the cohesin complex in myeloid neoplasms
Kon, A., Shih, L., Minamino, M., Sanada, M., Shiraishi, Y., Nagata, Y., Yoshida, K., Okuno, Y., Bando, M., Nakato, R., et al. (2013) · Nature Genetics · doi:10.1038/ng.2731 · Cited by 384 · see citing works
Self-citationUrbanski, L. M., Leclair, N. K., & Anczuków, O. (2018) · Wiley Interdisciplinary Reviews - RNA · doi:10.1002/wrna.1476 · Cited by 381 · see citing works
Obeng, E. A., Chappell, R. J., Seiler, M., Chen, M. C., Campagna, D. R., Schmidt, P. J., Schneider, R. K., Lord, A. M., Wang, L., Gambe, R. G., et al. (2016) · Cancer Cell · doi:10.1016/j.ccell.2016.08.006 · Cited by 380 · see citing works
MYC regulates the core pre-mRNA splicing machinery as an essential step in lymphomagenesis
Koh, C. M., Bezzi, M., Low, D. H. P., Ang, W. X., Teo, S. X., Gay, F. P. H., Al‐Haddawi, M., Tan, S., Osato, M., Sabò, A., et al. (2015) · Nature · doi:10.1038/nature14351 · Cited by 379 · see citing works
The landscape of somatic mutations in Down syndrome–related myeloid disorders
Yoshida, K., Toki, T., Okuno, Y., Kanezaki, R., Shiraishi, Y., Sato‐Otsubo, A., Sanada, M., Park, M.-J., Terui, K., Suzuki, H., et al. (2013) · Nature Genetics · doi:10.1038/ng.2759 · Cited by 377 · see citing works
Self-citationRossi, D., Bruscaggin, A., Spina, V., Rasi, S., Khiabanian, H., Messina, M., Fangazio, M., Vaisitti, T., Monti, S. M., Chiaretti, S., et al. (2011) · Blood · doi:10.1182/blood-2011-08-373159 · Cited by 372 · see citing works
Breaking bad: R-loops and genome integrity
Sollier, J., & Cimprich, K. A. (2015) · Trends in Cell Biology · doi:10.1016/j.tcb.2015.05.003 · Cited by 369 · see citing works
Germline ETV6 mutations in familial thrombocytopenia and hematologic malignancy
Zhang, M. Y., Churpek, J. E., Keel, S., Walsh, T., Lee, M. K., Loeb, K. R., Gülsüner, S., Pritchard, C. C., Sánchez-Bonilla, M., Delrow, J. J., et al. (2015) · Nature Genetics · doi:10.1038/ng.3177 · Cited by 368 · see citing works
Mutations in the spliceosome machinery, a novel and ubiquitous pathway in leukemogenesis
Makishima, H., Visconte, V., Sakaguchi, H., Jankowska, A. M., Kar, S. A., Jerez, A., Przychodzen, B. P., Bupathi, M., Guinta, K. M., Afable, M. G., et al. (2012) · Blood · doi:10.1182/blood-2011-12-399774 · Cited by 368 · see citing works
The genomic landscape of nasopharyngeal carcinoma
Lin, D., Meng, X., Hazawa, M., Nagata, Y., Varela, A. M., Xu, L., Sato, Y., Liu, L., Ding, L., Sharma, A., et al. (2014) · Nature Genetics · doi:10.1038/ng.3006 · Cited by 366 · see citing works
Self-citationOgawa, S. (2019) · Blood · doi:10.1182/blood-2018-10-844621 · Cited by 366 · see citing works
Self-citationSRSF1-Regulated Alternative Splicing in Breast Cancer
Anczuków, O., Akerman, M., Cléry, A., Wu, J., Shen, C., Shirole, N. H., Raimer, A. C., Sun, S., Jensen, M. A., Hua, Y., et al. (2015) · Molecular Cell · doi:10.1016/j.molcel.2015.09.005 · Cited by 362 · see citing works
The NLRP3 inflammasome functions as a driver of the myelodysplastic syndrome phenotype
Basiorka, A. A., McGraw, K. L., Eksioglu, E. A., Chen, X., Johnson, J., Zhang, L., Zhang, Q., Irvine, B. A., Cluzeau, T., Sallman, D. A., et al. (2016) · Blood · doi:10.1182/blood-2016-07-730556 · Cited by 356 · see citing works
Alternative tumour-specific antigens
Smith, C. C., Selitsky, S. R., Chai, S., Armistead, P. M., Vincent, B. G., & Serody, J. S. (2019) · Nature reviews. Cancer · doi:10.1038/s41568-019-0162-4 · Cited by 353 · see citing works
Yoshizato, T., Nannya, Y., Atsuta, Y., Shiozawa, Y., Iijima‐Yamashita, Y., Yoshida, K., Shiraishi, Y., Suzuki, H., Nagata, Y., Sato, Y., et al. (2017) · Blood · doi:10.1182/blood-2016-12-754796 · Cited by 351 · see citing works
Self-citationDoi, D., Magotani, H., Kikuchi, T., Ikeda, M., Hiramatsu, S., Yoshida, K., Amano, N., Nomura, M., Umekage, M., Morizane, A., et al. (2020) · Nature Communications · doi:10.1038/s41467-020-17165-w · Cited by 350 · see citing works
Self-citationUncovering novel mutational signatures by de novo extraction with SigProfilerExtractor
Islam, S. M. A., Díaz‐Gay, M., Wu, Y., Barnes, M. D., Vangara, R., Bergstrom, E. N., He, Y., Vella, M., Wang, J., Teague, J. W., et al. (2022) · Cell Genomics · doi:10.1016/j.xgen.2022.100179 · Cited by 350 · see citing works
Lee, S. C.-W., Dvinge, H., Kim, E. H., Cho, H., Micol, J., Chung, Y. R., Durham, B. H., Yoshimi, A., Kim, Y. J., Thomas, M., et al. (2016) · Nature Medicine · doi:10.1038/nm.4097 · Cited by 347 · see citing works
Widespread intron retention diversifies most cancer transcriptomes
Dvinge, H., & Bradley, R. K. (2015) · Genome Medicine · doi:10.1186/s13073-015-0168-9 · Cited by 346 · see citing works
The genetic basis of myelodysplasia and its clinical relevance
Cazzola, M., Porta, M. G. D., & Malcovati, L. (2013) · Blood · doi:10.1182/blood-2013-09-381665 · Cited by 345 · see citing works
The neurogenetics of alternative splicing
Vuong, C. K., Black, D. L., & Zheng, S. (2016) · Nature Reviews Neuroscience · doi:10.1038/nrn.2016.27 · Cited by 340 · see citing works
PRMTs and Arginine Methylation: Cancer’s Best-Kept Secret?
Jarrold, J., & Davies, C. C. (2019) · Trends in Molecular Medicine · doi:10.1016/j.molmed.2019.05.007 · Cited by 339 · see citing works
Targeting an RNA-Binding Protein Network in Acute Myeloid Leukemia
Wang, E., Lu, S. X., Pastore, A., Chen, X., Imig, J., Chun-Wei Lee, S., Hockemeyer, K., Ghebrechristos, Y. E., Yoshimi, A., Inoue, D., et al. (2019) · Cancer Cell · doi:10.1016/j.ccell.2019.01.010 · Cited by 338 · see citing works
SCF ubiquitin ligase-targeted therapies
Skaar, J. R., Pagan, J. K., & Pagano, M. (2014) · Nature Reviews Drug Discovery · doi:10.1038/nrd4432 · Cited by 336 · see citing works
Proteomic Investigations Reveal a Role for RNA Processing Factor THRAP3 in the DNA Damage Response
Beli, P., Lukashchuk, N., Wagner, S., Weinert, B. T., Olsen, J. V., Baskcomb, L., Mann, M., Jackson, S. P., & Choudhary, C. (2012) · Molecular Cell · doi:10.1016/j.molcel.2012.01.026 · Cited by 331 · see citing works
Such, E., Germing, U., Malcovati, L., Cervera, J., Kuendgen, A., Porta, M. G. D., Nomdedeu, B., Arenillas, L., Luño, E., Xicoy, B., et al. (2013) · Blood · doi:10.1182/blood-2012-08-452938 · Cited by 320 · see citing works
Green, M. R., Gentles, A. J., Nair, R. V., Irish, J. M., Kihira, S., Liu, C. L., Kela, I., Hopmans, E. S., Myklebust, J. H., Ji, H. P., et al. (2013) · Blood · doi:10.1182/blood-2012-09-457283 · Cited by 318 · see citing works
Myelodysplastic Syndromes Are Propagated by Rare and Distinct Human Cancer Stem Cells In Vivo
Woll, P. S., Kjällquist, U., Chowdhury, O., Doolittle, H., Wedge, D. C., Thongjuea, S., Erlandsson, R., Ngara, M., Anderson, K., Deng, Q., et al. (2014) · Cancer Cell · doi:10.1016/j.ccr.2014.03.036 · Cited by 317 · see citing works
- 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.
- Affiliations
- The University of Tokyo (JP)
- Institute of Medical Science, The University of Tokyo (JP)
- Heidelberg University (DE)
- Japan Science and Technology Agency (JP)
- University of Tsukuba (JP)
- Tokyo Metropolitan Ohtsuka Hospital (JP)
- SHOWA Medical University Fujigaoka Hospital (JP)
- Munich Leukemia Laboratory (Germany) (DE)
- Cedars-Sinai Medical Center (US)
- Chang Gung University (TW)
- Corresponding author
- Ogawa, Seishi
- ORCID
- Yoshida, Kenichi
- Sanada, Masashi
- Shiraishi, Yuichi
- Nowak, Daniel
- Nagata, Yasunobu
- Sato, Yusuke
- Kon, Ayana
- Nagasaki, Masao
- Suzuki, Yutaka
- Yamaguchi, Tomoyuki
- Otsu, Makoto
- Obara, Naoshi
- Ishiyama, Ken
- Nolte, Florian
- Miyawaki, Shuichi
- Sugano, Sumio
- Haferlach, Claudia
- Koeffler, H. Phillip
- Shih, Lee-Yung
- Haferlach, Torsten
- Chiba, Shigeru
- Nakauchi, Hiromitsu
- Miyano, Satoru
- Ogawa, Seishi
- Venue
- Nature
- Published
- 2011-09-11
- Volume
- 478
- Issue
- 7367
- Pages
- 64-69
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W2073889874
- Cited by
- 2,029
- References
- 37
- Citations by year
- 2026: 71 · 2025: 76 · 2024: 121 · 2023: 101 · 2022: 139 · 2021: 160 · 2020: 148 · 2019: 135 · 2018: 135 · 2017: 148 · 2016: 146 · 2015: 145 · 2014: 173 · 2013: 171 · 2012: 135
- FWCI
- 64.98
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature (publishedVersion)
- PubMed (publishedVersion)
- National University of Singapore (submittedVersion)
- RePEc: Research Papers in Economics (submittedVersion)
- Funders
- Japan Society for the Promotion of Science (22390191, 23791075, 22790895, 23659533, 23659482, 23390269, 23791068, 22659058)
- National Cancer Institute (R01CA026038)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
- Health Sciences › Medicine › Hematology › Acute Myeloid Leukemia Research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genomics and Rare Diseases
- Keywords
- myelodysplastic syndrome, splicing mutation, U2AF35, ZRSR2, SRSF2, SF3B1, 3' splice site recognition, pre-mRNA splicing, hematopoiesis, acute myeloid leukemia, myeloid neoplasms, aberrant splicing, therapeutic target
- MeSH terms
- Splicing Factor U2AF, Hematopoiesis, Humans, Mutation, Myelodysplastic Syndromes, Nuclear Proteins, Ribonucleoproteins, RNA Splicing, Spliceosomes, Alternative Splicing, Polymorphism, Single Nucleotide, RNA Splice Sites, Exome
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
