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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 (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 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. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted March 14, 2007 Accepted July 16, 2007 Prevalence and prognostic significance of allelic imbalance by single nucleotide polymorphism analysis in low risk myelodysplastic syndromes Azim Mohamedali, Joop Gaken, Natalie A Twine, Wendy Ingram, Nigel Westwood, Nicholas C Lea, Janet Hayden, Nora Donaldson, Carlo Aul, Norbert Gattermann, Aristotle Giagounidis, Ulrich Germing, Alan F. List, and Ghulam J. Mufti* Department of Haematological Medicine, Kings College London School of Medicine, London, United Kingdom Research and Development, King's College Hospital, London, United Kingdom Medizinische Klinik II, St. Johannes Hospital, Duisberg, Germany Department of Haematology, Oncology, and Clinical Immunology, Heinrich-Heine-University, Dusseldorf, Germany Department of Haematological Malignancies, H. Lee Moffitt Cancer Center and Research Institute, Tampa, FL, United States * Corresponding author; email: ghulam.mufti{at}kcl.ac.uk. 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 cytomorphological abnormalities in bone marrow and/or peripheral blood. High-resolution Single Nucleotide Polymorphism (SNP) genotyping microarrays allow detection of cytogenetically-cryptic genomic aberrations. We have studied 119 low risk MDS patients (RA=22; RCMD=51; RARS=12; RCMD-RS=12; 5q- Syndrome=16; 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 13% of 5q- Syndrome cases. Univariate analysis showed deletions (p=0.04) and IPSS (p<0.001) correlated with overall survival, however, on multivariate analysis only IPSS retained prognostic significance (p<0.001). We show, for the first time, that SNP-microarray analysis in low risk MDS patients reveals hitherto unrecognised UPD and CN changes which 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: A. Orazi and M. B. Czader Myelodysplastic Syndromes Am J Clin Pathol, August 1, 2009; 132(2): 290 - 305. [Abstract] [Full Text] [PDF] A. M. Jankowska, H. Szpurka, R. V. Tiu, H. Makishima, M. Afable, J. Huh, C. L. O'Keefe, R. Ganetzky, M. A. McDevitt, and J. P. Maciejewski Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms Blood, June 18, 2009; 113(25): 6403 - 6410. [Abstract] [Full Text] [PDF] F. Delhommeau, S. Dupont, V. D. Valle, C. James, S. Trannoy, A. Masse, O. Kosmider, J.-P. Le Couedic, F. Robert, A. Alberdi, et al. Mutation in TET2 in Myeloid Cancers N. Engl. J. Med., May 28, 2009; 360(22): 2289 - 2301. [Abstract] [Full Text] [PDF] M. Y. Follo, C. Finelli, C. Clissa, S. Mongiorgi, C. Bosi, G. Martinelli, M. Baccarani, L. Manzoli, A. M. Martelli, and L. Cocco Phosphoinositide-Phospholipase C {beta}1 Mono-Allelic Deletion Is Associated With Myelodysplastic Syndromes Evolution Into Acute Myeloid Leukemia J. Clin. Oncol., February 10, 2009; 27(5): 782 - 790. [Abstract] [Full Text] [PDF] A. J. Dunbar, L. P. Gondek, C. L. O'Keefe, H. Makishima, M. S. Rataul, H. Szpurka, M. A. Sekeres, X. F. Wang, M. A. McDevitt, and J. P. Maciejewski 250K Single Nucleotide Polymorphism Array Karyotyping Identifies Acquired Uniparental Disomy and Homozygous Mutations, Including Novel Missense Substitutions of c-Cbl, in Myeloid Malignancies Cancer Res., December 15, 2008; 68(24): 10349 - 10357. [Abstract] [Full Text] [PDF] 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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