DNMT3AMutations in Acute Myeloid Leukemia
| العنوان: | DNMT3AMutations in Acute Myeloid Leukemia |
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| المؤلفون: | Jasreet Hundal, Jacqueline E. Payton, Chris Harris, Timothy J. Ley, Jason Walker, Mark A. Watson, Cyriac Kandoth, Rakesh Nagarajan, Qunyuan Zhang, Ling Lin, Elaine R. Mardis, Joshua J. Conyers, Patricia A. Alldredge, Cheryl F. Lichti, Michael D. McLellan, Robert S. Fulton, John S. Welch, Daniel C. Link, Sean McGrath, William D. Shannon, Vincent Magrini, John R. Osborne, Sharon Heath, Joshua F. McMichael, Richard K. Wilson, Peter Westervelt, Li Ding, Tammi L. Vickery, Jack Baty, R. Reid Townsend, Tamara Lamprecht, Lisa Cook, Timothy A. Graubert, David J. Dooling, Nobish Varghese, Matthew J. Walter, Todd Wylie, Lucinda Fulton, Daniel C. Koboldt, John F. DiPersio, Joelle Kalicki, Gary W. Swift, Michelle O'Laughlin, Jerry P. Reed, Michael H. Tomasson, Kim D. Delehaunty, Heather Schmidt, David E. Larson |
| المصدر: | New England Journal of Medicine. 363:2424-2433 |
| بيانات النشر: | Massachusetts Medical Society, 2010. |
| سنة النشر: | 2010 |
| مصطلحات موضوعية: | Adult, Male, Oncology, medicine.medical_specialty, Myeloid, DNA Mutational Analysis, Gene Expression, medicine.disease_cause, Article, DNA Methyltransferase 3A, Frameshift mutation, Germline mutation, Internal medicine, medicine, Humans, Missense mutation, DNA (Cytosine-5-)-Methyltransferases, Frameshift Mutation, Proportional Hazards Models, Mutation, business.industry, Myeloid leukemia, General Medicine, Nucleic acid amplification technique, DNA Methylation, Middle Aged, Prognosis, medicine.disease, Survival Analysis, Leukemia, Myeloid, Acute, Leukemia, medicine.anatomical_structure, Karyotyping, embryonic structures, Cancer research, Female, business, Nucleic Acid Amplification Techniques |
| الوصف: | BACKGROUND The genetic alterations responsible for an adverse outcome in most patients with acute myeloid leukemia (AML) are unknown. METHODS Using massively parallel DNA sequencing, we identified a somatic mutation in DNMT3A, encoding a DNA methyltransferase, in the genome of cells from a patient with AML with a normal karyotype. We sequenced the exons of DNMT3A in 280 additional patients with de novo AML to define recurring mutations. RESULTS A total of 62 of 281 patients (22.1%) had mutations in DNMT3A that were predicted to affect translation. We identified 18 different missense mutations, the most common of which was predicted to affect amino acid R882 (in 37 patients). We also identified six frameshift, six nonsense, and three splice-site mutations and a 1.5-Mbp deletion encompassing DNMT3A. These mutations were highly enriched in the group of patients with an intermediate-risk cytogenetic profile (56 of 166 patients, or 33.7%) but were absent in all 79 patients with a favorable-risk cytogenetic profile (P |
| تدمد: | 1533-4406 0028-4793 |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::89cbaae4f0f83016a0a22f1187234244 https://doi.org/10.1056/nejmoa1005143 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....89cbaae4f0f83016a0a22f1187234244 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15334406 00284793 |
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