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Blood, 1 November 2007, Vol. 110, No. 9, pp. 3365-3373. Prepublished online as a Blood First Edition Paper on July 18, 2007; DOI 10.1182/blood-2007-03-079673.
NEOPLASIA Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes1 Department of Haematological Medicine, King's College London School of Medicine, London, United Kingdom; 2 Research and Development, King's College Hospital, London, United Kingdom; 3 St Johannes Hospital, Medizinische Klinik II, Duisberg, Germany; 4 Department of Haematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Düsseldorf, Germany; 5 H. Lee Moffitt Cancer Center and Research Institute, Department of Hematologic Malignancies, Tampa, FL Low-risk myelodysplastic syndrome (MDS) with normal cytogenetics accounts for approximately 50% of MDS patients. There are no pathognomonic markers in these cases and the diagnosis rests on cytomorphologic abnormalities in bone marrow and/or peripheral blood. Affymetrix high-resolution single-nucleotide polymorphism (SNP) genotyping microarrays allow detection of cytogenetically cryptic genomic aberrations. We have studied 119 low-risk MDS patients (refractory anemia [RA] = 22; refractory cytopenia with multilineage dysplasia [RCMD] = 51; refractory anemia with ringed sideroblasts [RARS] = 12; refractory cytopenia with multilineage dysplasia with ringed sideroblasts [RCMD-RS] = 12; 5q– syndrome = 16; refractory anemia with excess blasts [RAEB] = 6) using SNP microarrays to seek chromosomal markers undetected by conventional cytogenetics. Loss of heterozygosity (LOH) detected by 50K arrays was verified using 250K and 500K arrays. We demonstrate the presence of uniparental disomy (UPD) in 46%, deletions in 10%, and amplifications in 8% of cases. Copy number (CN) changes were acquired, whereas UPDs were also detected in constitutional DNA. UPD on 4q was identified in 25% of RARS, 12% of RCMD with normal cytogenetics, 17% of RAEB, and 6% of 5q– syndrome cases. Univariate analysis showed deletions (P = .04) and International Prognostic Scoring System (IPSS; P < .001) scores correlated with overall survival; however, on multivariate analysis only IPSS scores retained prognostic significance (P < .001). We show, for the first time, that SNP microarray analysis in low-risk MDS patients reveals hitherto unrecognized UPD and CN changes that may allow stratification of these patients for early therapeutic interventions.
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