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Blood, 18 June 2009, Vol. 113, No. 25, pp. 6403-6410. Prepublished online as a Blood First Edition Paper on April 16, 2009; DOI 10.1182/blood-2009-02-205690. This Article Full Text Full Text (PDF) All Versions of this Article: blood-2009-02-205690v1 113/25/6403    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 Jankowska, A. M. Articles by Maciejewski, J. P. PubMed PubMed Citation Articles by Jankowska, A. M. Articles by Maciejewski, J. P. Related Collections Myeloid Neoplasia Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  MYELOID NEOPLASIA Loss of heterozygosity 4q24 and TET2 mutations associated with myelodysplastic/myeloproliferative neoplasms Anna M. Jankowska1, Hadrian Szpurka1, Ramon V. Tiu1,2, Hideki Makishima1, Manuel Afable2, Jungwon Huh1,3, Christine L. O'Keefe1, Rebecca Ganetzky1, Michael A. McDevitt4, and Jaroslaw P. Maciejewski1,2 1 Department of Translational Hematology and Oncology Research, Taussig Cancer Institute, and 2 Department of Hematologic Oncology and Blood Disorders, Cleveland Clinic, OH; 3 Department of Laboratory Medicine, School of Medicine, Ewha Womans University, Seoul, South Korea; and 4 Divisions of Hematology and Hematological Malignancy, Departments of Medicine and Oncology, Johns Hopkins University School of Medicine, Baltimore, MD Chromosomal abnormalities are frequent in myeloid malignancies, but in most cases of myelodysplasia (MDS) and myeloproliferative neoplasms (MPN), underlying pathogenic molecular lesions are unknown. We identified recurrent areas of somatic copy number–neutral loss of heterozygosity (LOH) and deletions of chromosome 4q24 in a large cohort of patients with myeloid malignancies including MDS and related mixed MDS/MPN syndromes using single nucleotide polymorphism arrays. We then investigated genes in the commonly affected area for mutations. When we sequenced TET2, we found homozygous and hemizygous mutations. Heterozygous and compound heterozygous mutations were found in patients with similar clinical phenotypes without LOH4q24. Clinical analysis showed most TET2 mutations were present in patients with MDS/MPN (58%), including CMML (6/17) or sAML (32%) evolved from MDS/MPN and typical MDS (10%), suggesting they may play a ubiquitous role in malignant evolution. TET2 mutations affected conserved domains and the N terminus. TET2 is widely expressed in hematopoietic cells but its function is unknown, and it lacks homology to other known genes. The frequency of mutations in this candidate myeloid regulatory gene suggests an important role in the pathogenesis of poor prognosis MDS/MPN and sAML and may act as a disease gene marker for these often cytogenetically normal disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: O. Kosmider, V. Gelsi-Boyer, M. Cheok, S. Grabar, V. Della-Valle, F. Picard, F. Viguie, B. Quesnel, O. Beyne-Rauzy, E. Solary, et al. TET2 mutation is an independent favorable prognostic factor in myelodysplastic syndromes (MDSs) Blood, October 8, 2009; 114(15): 3285 - 3291. [Abstract] [Full Text] [PDF] C. Saint-Martin, G. Leroy, F. Delhommeau, G. Panelatti, S. Dupont, C. James, I. Plo, D. Bordessoule, C. Chomienne, A. Delannoy, et al. Analysis of the Ten-Eleven Translocation 2 (TET2) gene in familial myeloproliferative neoplasms Blood, August 20, 2009; 114(8): 1628 - 1632. [Abstract] [Full Text] [PDF]

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