Recurrent DNMT3A mutations in patients with myelodysplastic syndromes
| العنوان: | Recurrent DNMT3A mutations in patients with myelodysplastic syndromes |
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| المؤلفون: | Li Ding, Joelle Kalicki-Veizer, Heather Schmidt, Cyriac Kandoth, Peter Westervelt, Robert S. Fulton, Jin Shao, John F. DiPersio, Richard K. Wilson, Matthew J. Walter, Dong Shen, Timothy J. Ley, Elaine R. Mardis, Marcus Grillot, Michael D. McLellan, Michelle O'Laughlin, Timothy A. Graubert, Jack Baty |
| المصدر: | Leukemia |
| بيانات النشر: | Springer Science and Business Media LLC, 2011. |
| سنة النشر: | 2011 |
| مصطلحات موضوعية: | Male, Cancer Research, Myeloid, Methyltransferase, Kaplan-Meier Estimate, medicine.disease_cause, DNA Methyltransferase 3A, 0302 clinical medicine, hemic and lymphatic diseases, Granulocyte Precursor Cells, DNA (Cytosine-5-)-Methyltransferases, Aged, 80 and over, 0303 health sciences, Mutation, Myeloid leukemia, DNA, Neoplasm, Exons, Hematology, Middle Aged, Prognosis, 3. Good health, Leukemia, Myeloid, Acute, Leukemia, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, embryonic structures, DNA methylation, Disease Progression, Female, Adult, Biology, Article, Young Adult, 03 medical and health sciences, Myeloblast, medicine, Humans, Codon, Aged, 030304 developmental biology, Myelodysplastic syndromes, Sequence Analysis, DNA, DNA Methylation, medicine.disease, myelodysplastic syndrome, Myelodysplastic Syndromes, Immunology, DNMT3A, CpG Islands, mutation |
| الوصف: | Alterations in DNA methylation have been implicated in the pathogenesis of myelodysplastic syndromes (MDS), although the underlying mechanism remains largely unknown. Methylation of CpG dinucleotides is mediated by DNA methyltransferases, including DNMT1, DNMT3A and DNMT3B. DNMT3A mutations have recently been reported in patients with de novo acute myeloid leukemia (AML), providing a rationale for examining the status of DNMT3A in MDS samples. In this study, we report the frequency of DNMT3A mutations in patients with de novo MDS, and their association with secondary AML. We sequenced all coding exons of DNMT3A using DNA from bone marrow and paired normal cells from 150 patients with MDS and identified 13 heterozygous mutations with predicted translational consequences in 12/150 patients (8.0%). Amino acid R882, located in the methyltransferase domain of DNMT3A, was the most common mutation site, accounting for 4/13 mutations. DNMT3A mutations were expressed in the majority of cells in all tested mutant samples regardless of myeloblast counts, suggesting that DNMT3A mutations occur early in the course of MDS. Patients with DNMT3A mutations had worse overall survival compared with patients without DNMT3A mutations (P=0.005) and more rapid progression to AML (P=0.007), suggesting that DNMT3A mutation status may have prognostic value in de novo MDS. |
| تدمد: | 1476-5551 0887-6924 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::21147e99c46c8da4cbfd7dfb1352c8e1 https://doi.org/10.1038/leu.2011.44 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....21147e99c46c8da4cbfd7dfb1352c8e1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 14765551 08876924 |
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