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Blood, 1 February 2008, Vol. 111, No. 3, pp. 1534-1542.
Prepublished online as a Blood First Edition Paper on October 22, 2007; DOI 10.1182/blood-2007-05-092304.


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Submitted May 25, 2007
Accepted October 10, 2007

Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD and MDS-derived AML

Lukasz P Gondek, Ramon Tiu, Christine L O'Keefe, Mikkael A Sekeres, Karl S Theil, and Jaroslaw P Maciejewski*

Experimental Hematology and Hematopoiesis Section, Cleveland Clinic, Cleveland, OH, United States
Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, Cleveland, OH, United States
Taussig Cancer Center and Department of Clinical Pathology, Cleveland Clinic, Cleveland, OH, United States

* Corresponding author; email: maciejj{at}ccf.org.

Using metaphase cytogenetics (MC), chromosomal abnormalities are found only in a proportion of patients with MDS. We hypothesized that with new precise methods more cryptic karyotypic lesions can be uncovered that may show important clinical implications. We have applied 250K SNP arrays (SNP-A) to study chromosomal lesions in samples from 174 patients (94 MDS, 33 secondary AML and 47 MDS/MPD) and 76 controls. Using SNP-A, aberrations were found in around 3/4 of MDS, MDS/MPD and sAML (vs. 59%, 37%, 53% by MC; in 8% of patients MC was unsuccessful). Previously unrecognized lesions were detected in patients with normal MC and in those with known lesions. Moreover, segmental uniparental disomy (UPD) was found in 20% of MDS, 23% of sAML and 35% of MDS/MPD patients, a lesion resulting in copy-neutral loss of heterozygosity undetectable by MC. The potential clinical significance of abnormalities detected by SNP-A, but not seen on MC was demonstrated by their impact on overall survival. UPD involving chromosomes frequently affected by deletions may have prognostic implications similar to the deletions visible by MC. SNP-A-based karyotyping shows superior resolution for chromosomal defects, including UPD. This technique further complements MC to improve clinical prognosis and targeted therapies.


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