The DOI matches its Crossref record; 5 of the 5 references it cites were found in a registry or an index.
Whole-genome sequencing identifies recurrent mutations in chronic lymphocytic leukaemia
Open accessAbstract
Analysis of the genomes of four patients with chronic lymphocytic leukaemia, and validation in more than 300 patients, has identified four genes — NOTCH1, MYD88, XPO1 and KLHL6 — that are recurrently mutated in the condition. Mutations in NOTCH1, MYD88 and XPO1 are thought to contribute to the clinical evolution of the disease. Evidence that NOTCH1 and MYD88 mutations are activating events highlights them as potential therapeutic targets. Chronic lymphocytic leukaemia (CLL), the most frequent leukaemia in adults in Western countries, is a heterogeneous disease with variable clinical presentation and evolution1,2. Two major molecular subtypes can be distinguished, characterized respectively by a high or low number of somatic hypermutations in the variable region of immunoglobulin genes3,4. The molecular changes leading to the pathogenesis of the disease are still poorly understood. Here we performed whole-genome sequencing of four cases of CLL and identified 46 somatic mutations that potentially affect gene function. Further analysis of these mutations in 363 patients with CLL identified four genes that are recurrently mutated: notch 1 (NOTCH1), exportin 1 (XPO1), myeloid differentiation primary response gene 88 (MYD88) and kelch-like 6 (KLHL6). Mutations in MYD88 and KLHL6 are predominant in cases of CLL with mutated immunoglobulin genes, whereas NOTCH1 and XPO1 mutations are mainly detected in patients with unmutated immunoglobulins. The patterns of somatic mutation, supported by functional and clinical analyses, strongly indicate that the recurrent NOTCH1, MYD88 and XPO1 mutations are oncogenic changes that contribute to the clinical evolution of the disease. To our knowledge, this is the first comprehensive analysis of CLL combining whole-genome sequencing with clinical characteristics and clinical outcomes. It highlights the usefulness of this approach for the identification of clinically relevant mutations in cancer.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Fast and accurate short read alignment with Burrows-Wheeler transform
Li, H., & Durbin, R. (2009) · Bioinformatics · doi:10.1093/bioinformatics/btp324 · Cited by 58,607
Accurate whole human genome sequencing using reversible terminator chemistry
Bentley, D. R., Balasubramanian, S., Swerdlow, H. P., Smith, G. P., Milton, J., Brown, C. G., Hall, K. P., Evers, D. J., Barnes, C. L., Bignell, H. R., et al. (2008) · Nature · doi:10.1038/nature07517 · Cited by 3,684
The family of five: TIR-domain-containing adaptors in Toll-like receptor signalling
O'Neill, L. A. J., & Bowie, A. G. (2007) · Nature Reviews Immunology · doi:10.1038/nri2079 · Cited by 2,667
KEGG for representation and analysis of molecular networks involving diseases and drugs
Kanehisa, M., Goto, S., Furumichi, M., Tanabe, M., & Hirakawa, M. (2010) · Nucleic Acids Research · doi:10.1093/nar/gkp896 · Cited by 2,322
A comprehensive catalogue of somatic mutations from a human cancer genome
Pleasance, E. D., Cheetham, R. K., Stephens, P. J., McBride, D. J., Humphray, S. J., Greenman, C. D., Varela, I., Lin, M.-L., Ordóñez, G. R., Bignell, G. R., et al. (2010) · Nature · doi:10.1038/nature08658 · Cited by 1,696
Self-citation
Cited by
Signatures of mutational processes in human cancer
Initiative, A. P. C. G., Alexandrov, L. B., ICGC Breast Cancer Consortium, ICGC MMML-Seq Consortium, PedBrain, I., Nik-Zainal, S., Wedge, D. C., Aparicio, S. A. J. R., Behjati, S., Biankin, A. V., et al. (2013) · Nature · doi:10.1038/nature12477 · Cited by 9,660
Self-citationThe 2016 revision of the World Health Organization classification of lymphoid neoplasms
Swerdlow, S. H., Campo, E., Pileri, S. A., Harris, N. L., Stein, H., Siebert, R., Advani, R., Ghielmini, M., Salles, G. A., Zelenetz, A. D., et al. (2016) · Blood · doi:10.1182/blood-2016-01-643569 · Cited by 7,831
Self-citationLandscape of somatic mutations in 560 breast cancer whole-genome sequences
Nik-Zainal, S., Davies, H., Staaf, J., Ramakrishna, M., Glodzik, D., Zou, X., Martincorena, I., Alexandrov, L. B., Martin, S., Wedge, D. C., et al. (2016) · Nature · doi:10.1038/nature17676 · Cited by 2,218
Self-citationFrequent pathway mutations of splicing machinery in myelodysplasia
Yoshida, K., Sanada, M., Shiraishi, Y., Nowak, D., Nagata, Y., Yamamoto, R., Sato, Y., Sato-Otsubo, A., Kon, A., Nagasaki, M., et al. (2011) · Nature · doi:10.1038/nature10496 · Cited by 2,029
Clonal evolution in relapsed acute myeloid leukaemia revealed by whole-genome sequencing
Ding, L., Ley, T. J., Larson, D. E., Miller, C. A., Koboldt, D. C., Welch, J. S., Ritchey, J. K., Young, M. A., Lamprecht, T., McLellan, M. D., et al. (2012) · Nature · doi:10.1038/nature10738 · Cited by 1,993
High burden and pervasive positive selection of somatic mutations in normal human skin
Martincorena, I., Roshan, A., Gerstung, M., Ellis, P., Van Loo, P., McLaren, S., Wedge, D. C., Fullam, A., Alexandrov, L. B., Tubio, J. M., et al. (2015) · Science · doi:10.1126/science.aaa6806 · Cited by 1,770
Self-citationThe Life History of 21 Breast Cancers
Nik-Zainal, S., Van Loo, P., Wedge, D. C., Alexandrov, L. B., Greenman, C. D., Lau, K. W., Raine, K., Jones, D., Marshall, J., Ramakrishna, M., et al. (2012) · Cell · doi:10.1016/j.cell.2012.04.023 · Cited by 1,443
Self-citationSC3: consensus clustering of single-cell RNA-seq data
Kiselev, V. Y., Kirschner, K., Schaub, M. T., Andrews, T., Yiu, A., Chandra, T., Natarajan, K. N., Reik, W., Barahona, M., Green, A. R., et al. (2017) · Nature Methods · doi:10.1038/nmeth.4236 · Cited by 1,500
Evolution 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
Resistance Mechanisms for the Bruton's Tyrosine Kinase Inhibitor Ibrutinib
Woyach, J. A., Furman, R. R., Liu, T.-M., Ozer, H. G., Zapatka, M., Ruppert, A. S., Xue, L., Li, D. H.-H., Steggerda, S. M., Versele, M., et al. (2014) · New England Journal of Medicine · doi:10.1056/nejmoa1400029 · Cited by 1,275
JAKs and STATs in immunity, immunodeficiency, and cancer
O'Shea, J. J., Holland, S. M., & Staudt, L. M. (2013) · New England Journal of Medicine · doi:10.1056/nejmra1202117 · Cited by 927
Manz, M. G., & Boettcher, S. (2014) · Nature Reviews Immunology · doi:10.1038/nri3660 · Cited by 855
Role of Bruton’s tyrosine kinase in B cells and malignancies
Pal Singh, S., Dammeijer, F., & Hendriks, R. W. (2018) · Molecular Cancer · doi:10.1186/s12943-018-0779-z · Cited by 726
Chromatin organization is a major influence on regional mutation rates in human cancer cells
Schuster-Böckler, B., & Lehner, B. (2012) · Nature · doi:10.1038/nature11273 · Cited by 657
DICER1 loss and Alu RNA induce age-related macular degeneration via the NLRP3 inflammasome and MyD88
Tarallo, V., Hirano, Y., Gelfand, B. D., Dridi, S., Kerur, N., Kim, Y., Cho, W. G., Kaneko, H., Fowler, B. J., Bogdanovich, S., et al. (2012) · Cell · doi:10.1016/j.cell.2012.03.036 · Cited by 592
Mutational signatures: the patterns of somatic mutations hidden in cancer genomes
Alexandrov, L. B., & Stratton, M. R. (2014) · Current Opinion in Genetics & Development · doi:10.1016/j.gde.2013.11.014 · Cited by 488
Self-citationA targeted mutational landscape of angioimmunoblastic T-cell lymphoma
Odejide, O., Weigert, O., Lane, A. A., Toscano, D., Lunning, M. A., Kopp, N., Kim, S., van Bodegom, D., Bolla, S., Schatz, J. H., et al. (2014) · Blood · doi:10.1182/blood-2013-10-531509 · Cited by 398
The differential expression of IL-4 and IL-13 and its impact on type-2 immunity
Bao, K., & Reinhardt, R. L. (2015) · Cytokine · doi:10.1016/j.cyto.2015.05.008 · Cited by 316
PLCG1 mutations in cutaneous T-cell lymphomas
Vaqué, J. P., Gómez-López, G., Monsálvez, V., Varela, I., Martínez, N., Pérez, C., Domínguez, O., Graña, O., Rodríguez-Peralto, J. L., Rodríguez-Pinilla, S. M., et al. (2014) · Blood · doi:10.1182/blood-2013-05-504308 · Cited by 229
Self-citationPhenothiazines induce PP2A-mediated apoptosis in T cell acute lymphoblastic leukemia
Gutierrez, A., Pan, L., Groen, R. W. J., Baleydier, F., Kentsis, A., Marineau, J., Grebliunaite, R., Kozakewich, E., Reed, C., Pflumio, F., et al. (2014) · Journal of Clinical Investigation · doi:10.1172/jci65093 · Cited by 220
Ferreira, P. G., Jares, P., Rico, D., Gómez-López, G., Martínez-Trillos, A., Villamor, N., Ecker, S., González-Pérez, A., Knowles, D. G., Monlong, J., et al. (2014) · Genome Research · doi:10.1101/gr.152132.112 · Cited by 214
Self-citationA practical guide for mutational signature analysis in hematological malignancies
Maura, F., Degasperi, A., Nadeu, F., Leongamornlert, D., Davies, H., Moore, L., Royo, R., Ziccheddu, B., Puente, X. S., Avet-Loiseau, H., et al. (2019) · Nature Communications · doi:10.1038/s41467-019-11037-8 · Cited by 184
Self-citationMeyer, U. A., Zanger, U. M., & Schwab, M. (2013) · Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev-pharmtox-010510-100502 · Cited by 157
Brimer, N., Lyons, C., Wallberg, A. E., & Vande Pol, S. B. (2012) · Oncogene · doi:10.1038/onc.2011.589 · Cited by 133
Systems‐wide analysis of BCR signalosomes and downstream phosphorylation and ubiquitylation
Satpathy, S., Wagner, S. A., Beli, P., Gupta, R., Kristiansen, T. A., Malinova, D., Francavilla, C., Tolar, P., Bishop, G. A., Hostager, B. S., et al. (2015) · Molecular Systems Biology · doi:10.15252/msb.20145880 · Cited by 124
Understanding mutagenesis through delineation of mutational signatures in human cancer
Petljak, M., & Alexandrov, L. B. (2016) · Carcinogenesis · doi:10.1093/carcin/bgw055 · Cited by 110
NF-κB signaling pathway and its potential as a target for therapy in lymphoid neoplasms
Yu, L., Li, L., Medeiros, L. J., & Young, K. H. (2017) · Blood Reviews · doi:10.1016/j.blre.2016.10.001 · Cited by 105
Identification of cell-type-specific mutations in nodal t-cell lymphomas
Nguyen, T. B., Sakata-Yanagimoto, M., Asabe, Y., Matsubara, D., Kano, J., Yoshida, K., Shiraishi, Y., Chiba, K., Tanaka, H., Miyano, S., et al. (2017) · Blood Cancer Journal · doi:10.1038/bcj.2016.122 · Cited by 93
Hypermutation of the Inactive X Chromosome Is a Frequent Event in Cancer
Jäger, N., Schlesner, M., Jones, D. T. W., Raffel, S., Mallm, J.-P., Junge, K. M., Weichenhan, D., Bauer, T., Ishaque, N., Kool, M., et al. (2013) · Cell · doi:10.1016/j.cell.2013.09.042 · Cited by 90
The European Hematology Association Roadmap for European Hematology Research: a consensus document
Engert, A., Balduini, C., Brand, A., Coiffier, B., Cordonnier, C., Dohner, H., de Wit, T. D., Eichinger, S., Fibbe, W., Green, T., et al. (2016) · Haematologica · doi:10.3324/haematol.2015.136739 · Cited by 81
Stress and non-stress roles of inflammatory signals during HSC Emergence and maintenance
Clapes, T., Lefkopoulos, S., & Trompouki, E. (2016) · Frontiers in Immunology · doi:10.3389/fimmu.2016.00487 · Cited by 62
Gángó, A., Alpár, D., Galik, B., Marosvári, D., Kiss, R., Fésüs, V., Aczél, D., Eyüpoglu, E., Nagy, N., Nagy, Á., et al. (2020) · International Journal of Cancer · doi:10.1002/ijc.32502 · Cited by 54
Choi, J., Lee, K., Ingvarsdottir, K., Bonasio, R., Saraf, A., Florens, L., Washburn, M. P., Tadros, S., Green, M. R., & Busino, L. (2018) · Nature Cell Biology · doi:10.1038/s41556-018-0084-5 · Cited by 50
HDAC3 functions as a positive regulator in Notch signal transduction
Ferrante, F., Giaimo, B. D., Bartkuhn, M., Zimmermann, T., Close, V., Mertens, D., Nist, A., Stiewe, T., Meier-Soelch, J., Kracht, M., et al. (2020) · Nucleic Acids Research · doi:10.1093/nar/gkaa088 · Cited by 50
Guanine holes are prominent targets for mutation in cancer and inherited disease
Bacolla, A., Temiz, N. A., Yi, M., Ivanic, J., Cer, R. Z., Donohue, D. E., Ball, E. V., Mudunuri, U. S., Wang, G., Jain, A., et al. (2013) · PLoS Genetics · doi:10.1371/journal.pgen.1003816 · Cited by 40
Magistroni, V., Mauri, M., D’Aliberti, D., Mezzatesta, C., Crespiatico, I., Nava, M., Fontana, D., Sharma, N., Parker, W., Schreiber, A., et al. (2019) · Haematologica · doi:10.3324/haematol.2017.179937 · Cited by 29
Metadata
- Authors
- Puente, X. S., Pinyol, M., Quesada, V., Conde, L., Ordóñez, G. R., Villamor, N., Escaramis, G., Jares, P., Beà, S., González-Díaz, M., Bassaganyas, L., Baumann, T., Juan, M., López-Guerra, M., Colomer, D., Tubío, J. M. C., López, C., Navarro, A., Tornador, C., Aymerich, M., Rozman, M., Hernández, J. M., Puente, D. A., Freije, J. M. P., Velasco, G., Gutiérrez-Fernández, A., Costa, D., Carrió, A., Guijarro, S., Enjuanes, A., Hernández, L., Yagüe, J., Nicolás, P., Romeo-Casabona, C. M., Himmelbauer, H., Castillo, E., Dohm, J. C., de Sanjosé, S., Piris, M. A., de Alava, E., Miguel, J. S., Royo, R., Gelpí, J. L., Torrents, D., Orozco, M., Pisano, D. G., Valencia, A., Guigó, R., Bayés, M., Heath, S., Gut, M., Klatt, P., Marshall, J., Raine, K., Stebbings, L. A., Futreal, P. A., Stratton, M. R., Campbell, P. J., Gut, I., López-Guillermo, A., Estivill, X., Montserrat, E., López-Otín, C., & Campo, E.
- Venue
- Nature
- Published
- 2011-06-05
- Volume
- 475
- Issue
- 7354
- Pages
- 101-105
- ISSN
- 0028-0836 (ISSN-L)
- 1476-4687
- OpenAlex
- W1993355130
- Cited by
- 1,514
- References
- 5
- FWCI
- 82.89
- Type
- journal article
- Language
- en
- Open access
- hybrid
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
Data sources
Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.
