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Blood, 1 May 2008, Vol. 111, No. 9, pp. 4797-4808. Prepublished online as a Blood First Edition Paper on February 12, 2008; DOI 10.1182/blood-2007-09-113027. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-09-113027v1 111/9/4797    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via CrossRef Google Scholar Articles by Tomasson, M. H. Articles by Ley, T. J. PubMed PubMed Citation Articles by Tomasson, M. H. Articles by Ley, T. J. Related Collections Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Genomics Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia Michael H. Tomasson1, Zhifu Xiang1, Richard Walgren1, Yu Zhao1, Yumi Kasai2, Tracie Miner2, Rhonda E. Ries1, Olga Lubman3, Daved H. Fremont3, Michael D. McLellan2, Jacqueline E. Payton1, Peter Westervelt1, John F. DiPersio1, Daniel C. Link1, Matthew J. Walter1, Timothy A. Graubert1, Mark Watson3, Jack Baty4, Sharon Heath1, William D. Shannon1,4, Rakesh Nagarajan3, Clara D. Bloomfield5, Elaine R. Mardis2, Richard K. Wilson2, and Timothy J. Ley1 1 Department of Medicine, Division of Oncology; 2 Genome Sequencing Center; 3 Department of Pathology and Immunology; and 4 Division of Biostatistics, Siteman Cancer Center, all at Washington University School of Medicine, St Louis, MO; and 5 Cancer and Leukemia Group B, Ohio State University Comprehensive Cancer Center, Columbus Activating mutations in tyrosine kinase (TK) genes (eg, FLT3 and KIT) are found in more than 30% of patients with de novo acute myeloid leukemia (AML); many groups have speculated that mutations in other TK genes may be present in the remaining 70%. We performed high-throughput resequencing of the kinase domains of 26 TK genes (11 receptor TK; 15 cytoplasmic TK) expressed in most AML patients using genomic DNA from the bone marrow (tumor) and matched skin biopsy samples ("germline") from 94 patients with de novo AML; sequence variants were validated in an additional 94 AML tumor samples (14.3 million base pairs of sequence were obtained and analyzed). We identified known somatic mutations in FLT3, KIT, and JAK2 TK genes at the expected frequencies and found 4 novel somatic mutations, JAK1V623A, JAK1T478S, DDR1A803V, and NTRK1S677N, once each in 4 respective patients of 188 tested. We also identified novel germline sequence changes encoding amino acid substitutions (ie, nonsynonymous changes) in 14 TK genes, including TYK2, which had the largest number of nonsynonymous sequence variants (11 total detected). Additional studies will be required to define the roles that these somatic and germline TK gene variants play in AML pathogenesis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Hitchhikers' guide to the leukemia genome Nicholas C. P. Cross Blood 2008 111: 4428-4429. [Full Text] [PDF]

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