High-resolution genomic arrays facilitate detection of novel cryptic chromosomal lesions in myelodysplastic syndromes.
OBJECTIVE
Unbalanced chromosomal aberrations are common in myelodysplastic syndromes and have prognostic implications. An increased frequency of cytogenetic changes may reflect an inherent chromosomal instability due to failure of DNA repair. Therefore, it is likely that chromosomal defects in myelodysplastic syndromes may be more frequent than predicted by metaphase cytogenetics and new cryptic lesions may be revealed by precise analysis methods.


METHODS
We used a novel high-resolution karyotyping technique, array-based comparative genomic hybridization, to investigate the frequency of cryptic chromosomal lesions in a cohort of 38 well-characterized myelodysplastic syndromes patients; results were confirmed by microsatellite quantitative PCR or single nucleotide polymorphism analysis.


RESULTS
As compared to metaphase karyotyping, chromosomal abnormalities detected by array-based analysis were encountered more frequently and in a higher proportion of patients. For example, chromosomal defects were found in patients with a normal karyotype by traditional cytogenetics. In addition to verifying common abnormalities, previously cryptic defects were found in new regions of the genome. Cryptic changes often overlapped chromosomes and regions frequently identified as abnormal by metaphase cytogenetics.


CONCLUSIONS
The results underscore the instability of the myelodysplastic syndromes genome and highlight the utility of array-based karyotyping to study cryptic chromosomal changes which may provide new diagnostic information.
O'Keefe
Christine L
CL
Experimental Hematology and Hematopoiesis Section, Cleveland Clinic, Cleveland, Ohio 44195, USA.
Tiu
Ramon
R
Gondek
Lukasz P
LP
Powers
Jennifer
J
Theil
Karl S
KS
Kalaycio
Matt
M
Lichtin
Alan
A
Sekeres
Mikkael A
MA
Maciejewski
Jaroslaw P
JP
D000328:Adult; D000368:Aged; D002478:Cells, Cultured; D002869:Chromosome Aberrations; D015331:Cohort Studies; D020732:Cytogenetic Analysis / Q000379:methods; D005260:Female; D006801:Humans; D007621:Karyotyping; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats; D009190:Myelodysplastic Syndromes / Q000175:diagnosis / Q000235:genetics*; D009693:Nucleic Acid Hybridization / Q000379:methods; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods*; D016133:Polymerase Chain Reaction / Q000379:methods; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results