Detection of cryptic chromosomal lesions including acquired segmental uniparental disomy in advanced and low-risk myelodysplastic syndromes.

Abstract:

OBJECTIVES: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. CONCLUSION: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.

journal_name

Exp Hematol

journal_title

Experimental hematology

authors

Gondek LP,Haddad AS,O'Keefe CL,Tiu R,Wlodarski MW,Sekeres MA,Theil KS,Maciejewski JP

doi

10.1016/j.exphem.2007.08.009

subject

Has Abstract

pub_date

2007-11-01 00:00:00

pages

1728-38

issue

11

eissn

0301-472X

issn

1873-2399

pii

S0301-472X(07)00497-3

journal_volume

35

pub_type

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