Recurring mutations found by sequencing an acute myeloid leukemia genome
| Autor: | Li Ding, Anthony M. Brummett, Peter Westervelt, Jason Walker, Ken Chen, Jonathan K. Schindler, Mark A. Watson, Jerry S. Reed, Timothy J. Ley, Lynn K. Carmichael, Kim D. Delehaunty, Craig Pohl, Daniel C. Link, John W. Wallis, Michael D. McLellan, Jacqueline E. Payton, Richard K. Wilson, Rhonda E. Ries, Heather Schmidt, Tammi L. Vickery, Sean McGrath, Jolynda V. Ivy, Chris Harris, David E. Larson, Sharon Heath, Eric M. Clark, Devin P. Locke, Rick Meyer, Joelle Kalicki, Vincent Magrini, Scott M. Smith, Jody S. Robinson, Yuzhu Tang, Todd Wylie, Rakesh Nagarajan, Carrie A. Haipek, Adam F. Dukes, Madeline E. Wiechert, Gabriel E. Sanderson, Feiyu Du, Michael H. Tomasson, David J. Dooling, Glendoria Elliott, William D. Shannon, Rachel Abbott, Lucinda Fulton, John F. DiPersio, Joshua F. McMichael, Jack Baty, Xiaoqi Shi, Joshua Peck, Timothy A. Graubert, Ling Lin, Elaine R. Mardis, Robert S. Fulton, James M. Eldred, Matthew J. Walter, Daniel C. Koboldt |
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| Rok vydání: | 2009 |
| Předmět: |
Adult
Male DNA Mutational Analysis Enasidenib Biology medicine.disease_cause Genome Article Gene Frequency medicine Humans Point Mutation Gene Allele frequency Genetics Mutation Genome Human Point mutation Myeloid leukemia General Medicine Sequence Analysis DNA Middle Aged Isocitrate Dehydrogenase Leukemia Myeloid Acute Human genome Female Nucleophosmin |
| Zdroj: | The New England journal of medicine. 361(11) |
| ISSN: | 1533-4406 |
| Popis: | The full complement of DNA mutations that are responsible for the pathogenesis of acute myeloid leukemia (AML) is not yet known.We used massively parallel DNA sequencing to obtain a very high level of coverage (approximately 98%) of a primary, cytogenetically normal, de novo genome for AML with minimal maturation (AML-M1) and a matched normal skin genome.We identified 12 acquired (somatic) mutations within the coding sequences of genes and 52 somatic point mutations in conserved or regulatory portions of the genome. All mutations appeared to be heterozygous and present in nearly all cells in the tumor sample. Four of the 64 mutations occurred in at least 1 additional AML sample in 188 samples that were tested. Mutations in NRAS and NPM1 had been identified previously in patients with AML, but two other mutations had not been identified. One of these mutations, in the IDH1 gene, was present in 15 of 187 additional AML genomes tested and was strongly associated with normal cytogenetic status; it was present in 13 of 80 cytogenetically normal samples (16%). The other was a nongenic mutation in a genomic region with regulatory potential and conservation in higher mammals; we detected it in one additional AML tumor. The AML genome that we sequenced contains approximately 750 point mutations, of which only a small fraction are likely to be relevant to pathogenesis.By comparing the sequences of tumor and skin genomes of a patient with AML-M1, we have identified recurring mutations that may be relevant for pathogenesis. |
| Databáze: | OpenAIRE |
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