Acquired copy number alterations in adult acute myeloid leukemia genomes

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 obtain...

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Bibliographic Details
Published in:Proceedings of the National Academy of Sciences - PNAS 2009-08, Vol.106 (31), p.12950-12955
Main Authors: Walter, Matthew J, Payton, Jacqueline E, Ries, Rhonda E, Shannon, William D, Deshmukh, Hrishikesh, Zhao, Yu, Baty, Jack, Heath, Sharon, Westervelt, Peter, Watson, Mark A, Tomasson, Michael H, Nagarajan, Rakesh, O'Gara, Brian P, Bloomfield, Clara D, Mrózek, Krzysztof, Selzer, Rebecca R, Richmond, Todd A, Kitzman, Jacob, Geoghegan, Joel, Eis, Peggy S, Maupin, Rachel, Fulton, Robert S, McLellan, Michael, Wilson, Richard K, Mardis, Elaine R, Link, Daniel C, Graubert, Timothy A, DiPersio, John F, Ley, Timothy J
Format: Article
Language:English
Subjects:
Adult
Aged
Biological Sciences
Chromosomes
Comparative genomic hybridization
Cytogenetics
DNA
Female
Gene Dosage
Gene expression
Genes
Genetic mutation
Genome
Genomes
Genomics
Humans
Intracellular Signaling Peptides and Proteins - genetics
Leukemia
Leukemia, Myeloid, Acute - genetics
Male
Middle Aged
Mutation
Myeloid leukemia
Nuclear Pore Complex Proteins - genetics
Nuclear Proteins - genetics
Pathology
Polymorphism, Single Nucleotide
Ribonucleic acid
RNA
Translocation, Genetic
Tumors
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Summary: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
ISSN:0027-8424
1091-6490
DOI:10.1073/pnas.0903091106