Acquired copy number alterations in adult acute myeloid leukemia genomes.
Matthew J Walter, Jacqueline E Payton, Rhonda E Ries, William D Shannon, Hrishikesh Deshmukh, Yu Zhao, Jack Baty, Sharon Heath, Peter Westervelt, Mark A Watson, Michael H Tomasson, Rakesh Nagarajan, Brian P O'Gara, Clara D Bloomfield, Krzysztof Mrózek, Rebecca R Selzer, Todd A Richmond, Jacob Kitzman, Joel Geoghegan, Peggy S Eis, Rachel Maupin, Robert S Fulton, Michael McLellan, Richard K Wilson, Elaine R Mardis, Daniel C Link, Timothy A Graubert, John F DiPersio, Timothy J Ley
Author Information
Matthew J Walter: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
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 AMLpatients 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.
References
Blood. 2007 Aug 15;110(4):1251-61
[PMID: 17452517]
