Journal article
Acquired copy number alterations in adult acute myeloid leukemia genomes
Proceedings of the National Academy of Sciences - PNAS, Vol.106(31), pp.12950-12955
08/04/2009
DOI: 10.1073/pnas.0903091106
PMCID: PMC2716381
PMID: 19651600
Abstract
Cytogenetic analysis of acute myeloid leukemia (AML) cells has accelerated the identification of genes important for AML pathogenesis. To complement cytogenetic studies and to identify genes altered in AML genomes, we performed genome-wide copy number analysis with paired normal and tumor DNA obtained from 86 adult patients with de novo AML using 1.85 million feature SNP arrays. Acquired copy number alterations (CNAs) were confirmed using an ultra-dense array comparative genomic hybridization platform. A total of 201 somatic CNAs were found in the 86 AML genomes (mean, 2.34 CNAs per genome), with French-American-British system M6 and M7 genomes containing the most changes (10–29 CNAs per genome). Twenty-four percent of AML patients with normal cytogenetics had CNA, whereas 40% of patients with an abnormal karyotype had additional CNA detected by SNP array, and several CNA regions were recurrent. The mRNA expression levels of 57 genes were significantly altered in 27 of 50 recurrent CNA regions <5 megabases in size. A total of 8 uniparental disomy (UPD) segments were identified in the 86 genomes; 6 of 8 UPD calls occurred in samples with a normal karyotype. Collectively, 34 of 86 AML genomes (40%) contained alterations not found with cytogenetics, and 98% of these regions contained genes. Of 86 genomes, 43 (50%) had no CNA or UPD at this level of resolution. In this study of 86 adult AML genomes, the use of an unbiased high-resolution genomic screen identified many genes not previously implicated in AML that may be relevant for pathogenesis, along with many known oncogenes and tumor suppressor genes.
Details
- Title: Subtitle
- Acquired copy number alterations in adult acute myeloid leukemia genomes
- Creators
- Michael H Tomasson - Department of MedicineMatthew J Walter - Department of MedicineJacqueline E Payton - Department of Pathology and Immunology, andRhonda E Ries - Department of MedicineWilliam D Shannon - Department of MedicineHrishikesh Deshmukh - Department of Pathology and Immunology, andYu Zhao - Department of MedicineJack Baty - Division of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110Sharon Heath - Department of MedicinePeter Westervelt - Department of MedicineMark A Watson - Siteman Cancer CenterRakesh Nagarajan - Siteman Cancer CenterBrian P O'Gara - Department of MedicineClara D Bloomfield - Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210Krzysztof Mrózek - Division of Hematology and Oncology, Department of Medicine, Comprehensive Cancer Center, The Ohio State University, Columbus, OH 43210Rebecca R Selzer - Roche NimbleGen, Inc., Madison, WI 53719; andTodd A Richmond - Roche NimbleGen, Inc., Madison, WI 53719; andJacob Kitzman - Roche NimbleGen, Inc., Madison, WI 53719; andJoel Geoghegan - Roche NimbleGen, Inc., Madison, WI 53719; andPeggy S Eis - Roche NimbleGen, Inc., Madison, WI 53719; andRachel Maupin - The Genome Center, Washington University School of Medicine, St. Louis, MO 63110Robert S Fulton - The Genome Center, Washington University School of Medicine, St. Louis, MO 63110Michael McLellan - The Genome Center, Washington University School of Medicine, St. Louis, MO 63110Richard K Wilson - The Genome Center, Washington University School of Medicine, St. Louis, MO 63110Elaine R Mardis - The Genome Center, Washington University School of Medicine, St. Louis, MO 63110Daniel C Link - Department of MedicineTimothy A Graubert - Department of MedicineJohn F DiPersio - Department of MedicineTimothy J Ley - Department of Medicine
- Resource Type
- Journal article
- Publication Details
- Proceedings of the National Academy of Sciences - PNAS, Vol.106(31), pp.12950-12955
- DOI
- 10.1073/pnas.0903091106
- PMID
- 19651600
- PMCID
- PMC2716381
- NLM abbreviation
- Proc Natl Acad Sci U S A
- ISSN
- 0027-8424
- eISSN
- 1091-6490
- Publisher
- National Academy of Sciences
- Language
- English
- Date published
- 08/04/2009
- Academic Unit
- Hematology, Oncology, and Blood & Marrow Transplantation; Internal Medicine
- Record Identifier
- 9984094346002771
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