Publication

Acquired copy number alterations in adult acute myeloid leukemia genomes.

Proc Natl Acad Sci U S A. 2009 Aug 4;106(31):12950-5. Epub 2009 Jul 27.

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.

Authors

Walter MJ, Payton JE, Ries RE, Shannon WD, Deshmukh H, Zhao Y, Baty J, Heath S, Westervelt P, Watson MA, Tomasson MH, Nagarajan R, O'Gara BP, Bloomfield CD, Mrózek K, Selzer RR, Richmond TA, Kitzman J, Geoghegan J, Eis PS, Maupin R, Fulton RS, McLellan M, Wilson RK, Mardis ER, Link DC, Graubert TA, DiPersio JF, Ley TJ.