Disclosure of candidate genes in acute myeloid leukemia with complex karyotypes using microarray-based molecular characterization.
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.
Rücker
Frank G
FG
Department of Neural Information Processing, University Hospital of Ulm, Ulm, Germany.
Bullinger
Lars
L
Schwaenen
Carsten
C
Lipka
Daniel B
DB
Wessendorf
Swen
S
Fröhling
Stefan
S
Bentz
Martin
M
Miller
Simone
S
Scholl
Claudia
C
Schlenk
Richard F
RF
Radlwimmer
Bernhard
B
Kestler
Hans A
HA
Pollack
Jonathan R
JR
Lichter
Peter
P
Döhner
Konstanze
K
Döhner
Hartmut
H
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