Journal article
Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia
Blood, Vol.111(9), pp.4797-4808
Neoplasia
05/01/2008
DOI: 10.1182/blood-2007-09-113027
PMCID: PMC2343607
PMID: 18270328
Abstract
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,
JAK1
V623A
,
JAK1
T478S
,
DDR1
A803V
, and
NTRK1
S677N
, 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.
Details
- Title: Subtitle
- Somatic mutations and germline sequence variants in the expressed tyrosine kinase genes of patients with de novo acute myeloid leukemia
- Creators
- Michael H Tomasson - Department of Medicine, Division of OncologyZhifu Xiang - Department of Medicine, Division of OncologyRichard Walgren - Department of Medicine, Division of OncologyYu Zhao - Department of Medicine, Division of OncologyYumi Kasai - Genome Sequencing CenterTracie Miner - Genome Sequencing CenterRhonda E Ries - Department of Medicine, Division of OncologyOlga Lubman - Department of Pathology and Immunology; andDaved H Fremont - Department of Pathology and Immunology; andMichael D McLellan - Genome Sequencing CenterJacqueline E Payton - Department of Medicine, Division of OncologyPeter Westervelt - Department of Medicine, Division of OncologyJohn F DiPersio - Department of Medicine, Division of OncologyDaniel C Link - Department of Medicine, Division of OncologyMatthew J Walter - Department of Medicine, Division of OncologyTimothy A Graubert - Department of Medicine, Division of OncologyMark Watson - Department of Pathology and Immunology; andJack Baty - Division of Biostatistics, Siteman Cancer Center, all at Washington University School of Medicine, St Louis, MO; andSharon Heath - Department of Medicine, Division of OncologyWilliam D Shannon - Department of Medicine, Division of OncologyRakesh Nagarajan - Department of Pathology and Immunology; andClara D Bloomfield - Cancer and Leukemia Group B, Ohio State University Comprehensive Cancer Center, ColumbusElaine R Mardis - Genome Sequencing CenterRichard K Wilson - Genome Sequencing CenterTimothy J Ley - Department of Medicine, Division of Oncology
- Resource Type
- Journal article
- Publication Details
- Blood, Vol.111(9), pp.4797-4808
- Publisher
- American Society of Hematology
- Series
- Neoplasia
- DOI
- 10.1182/blood-2007-09-113027
- PMID
- 18270328
- PMCID
- PMC2343607
- ISSN
- 0006-4971
- eISSN
- 1528-0020
- Language
- English
- Date published
- 05/01/2008
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094529702771
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