The DOI matches its Crossref record; 27 of the 27 references it cites were found in a registry or an index.
Next-Generation Sequencing Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in TET2, CBL, RAS, and RUNX1
Abstract
Purpose: Chronic myelomonocytic leukemia (CMML) is a clonal hematopoietic malignancy that is characterized by features of both a myeloproliferative neoplasm and a myelodysplastic syndrome. Thus far, data on a comprehensive cytogenetic or molecular genetic characterization are limited. Patients and Methods: Here, we analyzed 81 thoroughly characterized patients with CMML (CMML type 1, n = 45; CMML type 2, n = 36) by applying next-generation sequencing (NGS) technology to investigate CBL, JAK2, MPL, NRAS, and KRAS at known mutational hotspot regions. In addition, complete coding regions were analyzed for RUNX1 (β isoform) and TET2 aberrations. Results: Cytogenetic aberrations were found in 18.2% of patients (14 of 77 patients). In contrast, at least one molecular mutation was observed in 72.8% of patients (59 of 81 patients). A mean of 1.6 mutations per patient was observed by this unprecedented screening. In total, 105 variances were detected by this comprehensive molecular screening. After excluding known polymorphisms or silent mutations, 82 distinct mutations remained (CBL, n = 15; JAK2V617F, n = 8; MPL, n = 0; NRAS, n = 10; KRAS, n = 12; RUNX1, n = 7; and TET2, n = 41). With respect to clinical data, a better outcome was seen for patients carrying TET2 mutations (P = .013). Conclusion: The number of molecular markers used to categorize myeloid neoplasms is constantly increasing. Here, NGS screening has been demonstrated to support a comprehensive characterization of the molecular background in CMML. A pattern of molecular mutations translates into different biologic and prognostic categories of CMML.
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Cites
WHO Classification of Tumours of Haematopoietic and Lymphoid Tissues
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Genome sequencing in microfabricated high-density picolitre reactors
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Mutation in TET2 in Myeloid Cancers
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Next-Generation Sequencing: From Basic Research to Diagnostics
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Genetic characterization of TET1, TET2, and TET3 alterations in myeloid malignancies
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Acquired mutations in TET2 are common in myelodysplastic syndromes
Langemeijer, S. M. C., Kuiper, R. P., Berends, M., Knops, R., Aslanyan, M. G., Massop, M., Stevens-Linders, E., van Hoogen, P., van Kessel, A. G., Raymakers, R. A. P., et al. (2009) · Nature Genetics · doi:10.1038/ng.391 · Cited by 680
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Cited by
Quivoron, C., Couronné, L., Della Valle, V., Lopez, C. K., Plo, I., Wagner-Ballon, O., Do Cruzeiro, M., Delhommeau, F., Arnulf, B., Stern, M.-H., et al. (2011) · Cancer Cell · doi:10.1016/j.ccr.2011.06.003 · Cited by 924
Elena, C., Gallì, A., Such, E., Meggendorfer, M., Germing, U., Rizzo, E., Cervera, J., Molteni, E., Fasan, A., Schuler, E., et al. (2016) · Blood · doi:10.1182/blood-2016-05-714030 · Cited by 361
Self-citationTet2 restrains inflammatory gene expression in macrophages
Cull, A. H., Snetsinger, B., Buckstein, R., Wells, R. A., & Rauh, M. J. (2017) · Experimental Hematology · doi:10.1016/j.exphem.2017.08.001 · Cited by 295
The Ten-Eleven Translocation-2 (TET2) gene in hematopoiesis and hematopoietic diseases
Solary, E., Bernard, O. A., Tefferi, A., Fuks, F., & Vainchenker, W. (2014) · Leukemia · doi:10.1038/leu.2013.337 · Cited by 288
Aucagne, R., Droin, N., Paggetti, J., Lagrange, B., Largeot, A., Hammann, A., Bataille, A., Martin, L., Yan, K.-P., Fenaux, P., et al. (2011) · Journal of Clinical Investigation · doi:10.1172/jci45213 · Cited by 117
Metadata
- Authors
- Kohlmann, A., Grossmann, V., Klein, H.-U., Schindela, S., Weiss, T., Kazak, B., Dicker, F., Schnittger, S., Dugas, M., Kern, W., Haferlach, C., & Haferlach, T.
- Venue
- Journal of Clinical Oncology
- Published
- 2010-08-20
- Volume
- 28
- Issue
- 24
- Pages
- 3858-3865
- ISSN
- 0732-183X (ISSN-L)
- 1527-7755
- OpenAlex
- W2127332345
- Cited by
- 299
- References
- 27
- FWCI
- 22.27
- Type
- journal article
- Language
- en
- Open access
- closed
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- Kohlmann, A., Grossmann, V., Klein, H.-U., Schindela, S., Weiss, T., Kazak, B., Dicker, F., Schnittger, S., Dugas, M., Kern, W., Haferlach, C., & Haferlach, T. (2010). Next-Generation Sequencing Technology Reveals a Characteristic Pattern of Molecular Mutations in 72.8% of Chronic Myelomonocytic Leukemia by Detecting Frequent Alterations in TET2, CBL, RAS, and RUNX1. Journal of Clinical Oncology. https://doi.org/10.1200/jco.2009.27.1361
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