title: Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization.
abstract: OBJECTIVE
  To identify novel genomic regions of interest in acute myeloid leukemia (AML) with complex karyotypes, we applied comparative genomic hybridization to microarrays (array-CGH), allowing high-resolution genome-wide screening of genomic imbalances.
  
  
  METHODS
  Sixty AML cases with complex karyotypes were analyzed using array-CGH; parallel analysis of gene expression was performed in a subset of cases.
  
  
  RESULTS
  Genomic losses were found more frequently than gains. The most frequent losses affected 5q (77%), 17p (55%), and 7q (45%), and the most frequent genomic gains 11q (40%) and 8q (38%). Critical segments could be delineated to genomic fragments of only 0.8 to a few megabase-pairs of DNA. In lost/gained regions, gene expression profiling detected a gene dosage effect with significant lower/higher average gene expression levels across the genes located in the respective regions. Furthermore, high-level DNA amplifications were identified in several regions: 11q23.3-q24.1 (n = 7), 21q22 (n = 6), 11q23.3 (n = 5), 13q12 (n = 3), 8q24 (n = 3), 9p24 (n = 2), 12p13 (n = 2), and 20q11 (n = 2). Parallel analysis of gene expression in critical amplicons displayed overexpressed candidate genes (eg, C8FW and MYC in 8q24).
  
  
  CONCLUSIONS
  In conclusion, a large spectrum of genomic imbalances, including novel recurring changes in AML with complex karyotypes, was identified using array-CGH. In addition, the combined analysis of array-CGH data with gene expression profiles allowed the detection of candidate genes involved in the pathogenesis of AML.
authors.affiliation: Department of Neural Information Processing, University Hospital of Ulm, Ulm, Germany.
authors.forename: Frank G
authors.initials: FG
authors.lastname: Rücker
authors.forename: Lars
authors.initials: L
authors.lastname: Bullinger
authors.forename: Carsten
authors.initials: C
authors.lastname: Schwaenen
authors.forename: Daniel B
authors.initials: DB
authors.lastname: Lipka
authors.forename: Swen
authors.initials: S
authors.lastname: Wessendorf
authors.forename: Stefan
authors.initials: S
authors.lastname: Fröhling
authors.forename: Martin
authors.initials: M
authors.lastname: Bentz
authors.forename: Simone
authors.initials: S
authors.lastname: Miller
authors.forename: Claudia
authors.initials: C
authors.lastname: Scholl
authors.forename: Richard F
authors.initials: RF
authors.lastname: Schlenk
authors.forename: Bernhard
authors.initials: B
authors.lastname: Radlwimmer
authors.forename: Hans A
authors.initials: HA
authors.lastname: Kestler
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Pollack
authors.forename: Peter
authors.initials: P
authors.lastname: Lichter
authors.forename: Konstanze
authors.initials: K
authors.lastname: Döhner
authors.forename: Hartmut
authors.initials: H
authors.lastname: Döhner
mesh_terms: D000208:Acute Disease; D022981:Allelic Imbalance; D002869:Chromosome Aberrations; D002880:Chromosomes, Human, Pair 11; D002886:Chromosomes, Human, Pair 17; D002890:Chromosomes, Human, Pair 20; D002895:Chromosomes, Human, Pair 5; D002897:Chromosomes, Human, Pair 7; D002898:Chromosomes, Human, Pair 8; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D008040:Genetic Linkage; D042822:Genomic Instability; D006801:Humans; D007621:Karyotyping; D007951:Leukemia, Myeloid / Q000235:genetics*; D019656:Loss of Heterozygosity; D046228:Microarray Analysis; D021141:Nucleic Acid Amplification Techniques; D009693:Nucleic Acid Hybridization