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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. This Article Full Text Full Text (PDF) Supplemental Methods and Tables All Versions of this Article: blood-2007-03-079673v1 110/9/3365    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Mohamedali, A. Articles by Mufti, G. J. Search for Related Content PubMed PubMed Citation Articles by Mohamedali, A. Articles by Mufti, G. J. Related Collections Oncogenes and Tumor Suppressors Clinical Trials and Observations Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Prevalence and prognostic significance of allelic imbalance by single-nucleotide polymorphism analysis in low-risk myelodysplastic syndromes Azim Mohamedali1, Joop Gäken1, Natalie A. Twine1, Wendy Ingram1, Nigel Westwood1, Nicholas C. Lea1, Janet Hayden1, Nora Donaldson2, Carlo Aul3, Norbert Gattermann4, Aristotle Giagounidis4, Ulrich Germing4, Alan F. List5, and Ghulam J. Mufti1 1 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. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: L. Wang, C. Fidler, N. Nadig, A. Giagounidis, M. G. Della Porta, L. Malcovati, S. Killick, N. Gattermann, C. Aul, J. Boultwood, et al. Genome-wide analysis of copy number changes and loss of heterozygosity in myelodysplastic syndrome with del(5q) using high-density single nucleotide polymorphism arrays Haematologica, July 1, 2008; 93(7): 994 - 1000. [Abstract] [Full Text] [PDF] L. P. Gondek, R. Tiu, C. L. O'Keefe, M. A. Sekeres, K. S. Theil, and J. P. Maciejewski Chromosomal lesions and uniparental disomy detected by SNP arrays in MDS, MDS/MPD, and MDS-derived AML Blood, February 1, 2008; 111(3): 1534 - 1542. [Abstract] [Full Text] [PDF]

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