Genome-wide DNA-mapping of CD34+ cells from patients with myelodysplastic syndrome using 500K SNP arrays identifies significant regions of deletion and uniparental disomy.
OBJECTIVE
Identification of genomic lesions in progenitor cells of patients with myelodysplastic syndrome (MDS) could lead to the discovery of new disease-specific genes and may be of prognostic value.


METHODS
We carried out a genome-wide mapping of DNA from CD34+ cells of MDS patients with high-resolution 500K single nucleotide polymorphism arrays and a concomitant integration with global gene expression analysis. Thirteen MDS patients were analyzed.


RESULTS
Copy number and loss of heterozygosity analyses detected heterozygous deletions on chromosomes 2, 9, 13, 16, 17, and 20 ranging in size from 0.1 megabases (Mba) to 2.1 Mba. Additionally, numerous regions with significant uniparental disomy were detected. Integration of the genomic data with gene expression analysis showed that genes, which were downregulated at least 1.5-fold in regions of significant deletion and uniparental disomy were exclusively downregulated in those samples displaying the aberration. Genomics and gene expression data were confirmed by real-time polymerase chain reaction and variable number tandem repeat analysis.


CONCLUSIONS
High-density genomic mapping of CD34+ bone marrow cells from patients with MDS identifies cryptic genetic lesions and offers new opportunities for the discovery of target genes in MDS by integration with gene expression analysis.
Nowak
Daniel
D
Department of Hematology and Oncology, Charité University Hospital, Campus Benjamin Franklin, Berlin, Germany. Daniel.Nowak@cshs.org
Nolte
Florian
F
Mossner
Maximilian
M
Nowak
Verena
V
Baldus
Claudia D
CD
Hopfer
Olaf
O
Noll
Stefanie
S
Thiel
Eckhard
E
Wagner
Florian
F
Hofmann
Wolf-Karsten
WK
D000328:Adult; D000368:Aged; D018952:Antigens, CD34; D001483:Base Sequence; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics; D005260:Female; D005786:Gene Expression Regulation; D015894:Genome, Human; D006801:Humans; D008297:Male; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics* / Q000378:metabolism*; D020641:Polymorphism, Single Nucleotide; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D013234:Stem Cells / Q000378:metabolism*
D018952:Antigens, CD34