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Blood, 15 October 2008, Vol. 112, No. 8, pp. 3412-3424. Prepublished online as a Blood First Edition Paper on July 28, 2008; DOI 10.1182/blood-2007-11-122028. This Article Full Text Full Text (PDF) Supplemental Tables and Figures All Versions of this Article: blood-2007-11-122028v1 112/8/3412    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 CrossRef Citing Articles via Google Scholar Google Scholar Articles by Starczynowski, D. T. Articles by Karsan, A. Search for Related Content PubMed PubMed Citation Articles by Starczynowski, D. T. Articles by Karsan, A. Related Collections Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA High-resolution whole genome tiling path array CGH analysis of CD34+ cells from patients with low-risk myelodysplastic syndromes reveals cryptic copy number alterations and predicts overall and leukemia-free survival Daniel T. Starczynowski1,2, Suzanne Vercauteren2, Adele Telenius3, Sandy Sung1, Kaoru Tohyama4, Angela Brooks-Wilson57, John J. Spinelli8, Connie J. Eaves2,9,10, Allen C. Eaves2,9,10, Douglas E. Horsman2,3, Wan L. Lam2,11, and Aly Karsan13,9 1 Department of Medical Biophysics, British Columbia Cancer Agency, Vancouver; 2 Department of Pathology and Laboratory Medicine, University of British Columbia, Vancouver; 3 Department of Pathology and Laboratory Medicine, British Columbia Cancer Agency, Vancouver; 4 Clinical Pathology and Laboratory Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan; 5 Department of Healthcare and Epidemiology, University of British Columbia, Vancouver; 6 Genome Sciences Center, British Columbia Cancer Agency, Vancouver; 7 Department of Medical Genetics, University of British Columbia, Vancouver; 8 Department of Cancer Control Research and 9 Terry Fox Laboratory, British Columbia Cancer Agency, Vancouver; 10 Department of Medicine, University of British Columbia, Vancouver; and 11 Department of Cancer Genetics and Developmental Biology, British Columbia Cancer Agency, Vancouver Myelodysplastic syndromes (MDSs) pose an important diagnostic and treatment challenge because of the genetic heterogeneity and poorly understood biology of the disease. To investigate initiating genomic alterations and the potential prognostic significance of cryptic genomic changes in low-risk MDS, we performed whole genome tiling path array comparative genomic hybridization (aCGH) on CD34+ cells from 44 patients with an International Prognostic Scoring System score less than or equal to 1.0. Clonal copy number differences were detected in cells from 36 of 44 patients. In contrast, cells from only 16 of the 44 patients displayed karyotypic abnormalities. Although most patients had normal karyotype, aCGH identified 21 recurring copy number alterations. Examples of frequent cryptic alterations included gains at 11q24.2-qter, 17q11.2, and 17q12 and losses at 2q33.1-q33.2, 5q13.1-q13.2, and 10q21.3. Maintenance of genomic integrity defined as less than 3 Mb total disruption of the genome correlated with better overall survival (P = .002) and was less frequently associated with transformation to acute myeloid leukemia (P = .033). This study suggests a potential role for the use of aCGH in the clinical workup of MDS patients. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

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