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Blood, 30 July 2009, Vol. 114, No. 5, pp. 1038-1045. Prepublished online as a Blood First Edition Paper on June 3, 2009; DOI 10.1182/blood-2008-12-192039. This Article Full Text Full Text (PDF) Supplemental Appendices and Tables All Versions of this Article: blood-2008-12-192039v1 114/5/1038    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 Google Scholar Articles by Tosello, V. Articles by Ferrando, A. A. PubMed PubMed Citation Articles by Tosello, V. Articles by Ferrando, A. A. Related Collections Lymphoid Neoplasia Clinical Trials and Observations Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA WT1 mutations in T-ALL Valeria Tosello1, Marc R. Mansour2, Kelly Barnes1, Maddalena Paganin3, Maria Luisa Sulis1,4, Sarah Jenkinson2, Christopher G. Allen2, Rosemary E. Gale2, David C. Linch2, Teresa Palomero1,5, Pedro Real1,6, Vundavalli Murty1, Xiaopan Yao7, Susan M. Richards8, Anthony Goldstone9, Jacob Rowe10, Giuseppe Basso3, Peter H. Wiernik11,12, Elisabeth Paietta11,12, Rob Pieters13,14, Martin Horstmann15,16, Jules P. P. Meijerink13, and Adolfo A. Ferrando1,4,5 1 Institute for Cancer Genetics, Columbia University, New York, NY; 2 Cancer Institute, Department of Haematology, University College London, London, United Kingdom; 3 Hemato-Oncology Laboratory, Department of Pediatrics, University of Padua, Padua, Italy; Departments of 4 Pediatrics and 5 Pathology, Columbia University Medical Center, New York, NY; 6 Andalusian Stem Cell Bank, Centro de Investigacion Biomedica, Granada, Spain; 7 Department of Biostatistics & Computational Biology, Dana-Farber Cancer Institute, Boston, MA; 8 Clinical Trial Service Unit, Oxford, United Kingdom; 9 University College London Hospitals, London, United Kingdom; 10 Rambam Medical Center and Technion, Israel Institute of Technology, Haifa, Israel; 11 Montefiore Medical Center North, Bronx, NY; 12 New York Medical College, New York, NY; 13 Department of Pediatric Oncology/Hematology, Erasmus MC–Sophia Children's Hospital, Rotterdam, The Netherlands; 14 Dutch Childhood Oncology Group, The Hague, The Netherlands; 15 Clinic for Pediatric Hematology and Oncology, University Hospital Hamburg-Eppendorf, Hamburg, Germany; and 16 German Cooperative Study Group for Childhood Acute Lymphoblastic Leukemia, Hamburg, Germany The molecular mechanisms involved in disease progression and relapse in T-cell acute lymphoblastic leukemia (T-ALL) are poorly understood. We used single nucleotide polymorphism array analysis to analyze paired diagnostic and relapsed T-ALL samples to identify recurrent genetic alterations in T-ALL. This analysis showed that diagnosis and relapsed cases have common genetic alterations, but also that relapsed samples frequently lose chromosomal markers present at diagnosis, suggesting that relapsed T-ALL emerges from an ancestral clone different from the major leukemic population at diagnosis. In addition, we identified deletions and associated mutations in the WT1 tumor suppressor gene in 2 of 9 samples. Subsequent analysis showed WT1 mutations in 28 of 211 (13.2%) of pediatric and 10 of 85 (11.7%) of adult T-ALL cases. WT1 mutations present in T-ALL are predominantly heterozygous frameshift mutations resulting in truncation of the C-terminal zinc finger domains of this transcription factor. WT1 mutations are most prominently found in T-ALL cases with aberrant rearrangements of the oncogenic TLX1, TLX3, and HOXA transcription factor oncogenes. Survival analysis demonstrated that WT1 mutations do not confer adverse prognosis in pediatric and adult T-ALL. Overall, these results identify the presence of WT1 mutations as a recurrent genetic alteration in T-ALL. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: C. G. Mullighan Mutations of NOTCH1, FBXW7, and prognosis in T-lineage acute lymphoblastic leukemia Haematologica, October 1, 2009; 94(10): 1338 - 1340. [Full Text] [PDF]

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