Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.
OBJECTIVE
Using metaphase cytogenetics (MC), chromosomal defects can be detected in 40% to 60% of patients with myelodysplastic syndromes (MDS); cytogenetic results have a major impact on prognosis. We hypothesize that more precise methods of chromosomal analysis will detect new/additional cryptic lesions in a higher proportion of MDS patients.


METHODS
We have applied single nucleotide polymorphism microarrays (SNP-A) to perform high-resolution karyotyping in MDS to determine gene copy number and detect loss of heterozygosity (LOH).


RESULTS
Using this method, chromosomal defects were found in 82% of MDS patients vs 50% as measured by MC; lesions were present in 68% of patients with normal MC, while in 81% of those with abnormal MC, new aberrations were found. In addition to gains or losses of chromosomal material, areas of LOH due to segmental uniparental disomy were found in 33% of patients.


CONCLUSIONS
SNP-A findings demonstrate that chromosomal lesions are present in a much higher proportion of patients than predicted by traditional cytogenetics. These lesions may reflect an underlying generalized chromosomal instability in MDS. Additional previously cryptic defects may explain the clinical variability of MDS. New lesions may have important prognostic implications, suggesting that, in the future, SNP-A-based karyotyping may complement MC in laboratory evaluation of MDS.
Gondek
Lukasz P
LP
Experimental Hematology and Hematopoiesis Section, Taussig Cancer Center, Cleveland Clinic, Cleveland, OH 44195, USA.
Haddad
Abdo S
AS
O'Keefe
Christine L
CL
Tiu
Ramon
R
Wlodarski
Marcin W
MW
Sekeres
Mikkael A
MA
Theil
Karl S
KS
Maciejewski
Jaroslaw P
JP
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D002869:Chromosome Aberrations; D018628:Gene Dosage; D006801:Humans; D007621:Karyotyping / Q000379:methods*; D019656:Loss of Heterozygosity; D008875:Middle Aged; D009190:Myelodysplastic Syndromes / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D020641:Polymorphism, Single Nucleotide; D024182:Uniparental Disomy