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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.
- Source :
-
Journal of clinical oncology : official journal of the American Society of Clinical Oncology [J Clin Oncol] 2010 Aug 20; Vol. 28 (24), pp. 3858-65. Date of Electronic Publication: 2010 Jul 19. - Publication Year :
- 2010
-
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.<br />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 (beta isoform) and TET2 aberrations.<br />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).<br />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.
- Subjects :
- Adult
Aged
Dioxygenases
Female
Genes, ras
Humans
Kaplan-Meier Estimate
Male
Middle Aged
Predictive Value of Tests
Prognosis
Core Binding Factor Alpha 2 Subunit genetics
DNA-Binding Proteins genetics
Leukemia, Myelomonocytic, Chronic genetics
Mutation
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-cbl genetics
Sequence Analysis, DNA methods
ras Proteins genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1527-7755
- Volume :
- 28
- Issue :
- 24
- Database :
- MEDLINE
- Journal :
- Journal of clinical oncology : official journal of the American Society of Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 20644105
- Full Text :
- https://doi.org/10.1200/JCO.2009.27.1361