SEARCH:   Advanced

Blood, 6 August 2009, Vol. 114, No. 6, pp. 1236-1242. Prepublished online as a Blood First Edition Paper on May 7, 2009; DOI 10.1182/blood-2009-03-209759. This Article Full Text Full Text (PDF) Supplemental Methods, Table, and Figure All Versions of this Article: blood-2009-03-209759v1 114/6/1236    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 Ritz, O. Articles by Leroy, K. PubMed PubMed Citation Articles by Ritz, O. Articles by Leroy, K. Related Collections Lymphoid Neoplasia Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  LYMPHOID NEOPLASIA Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma Olga Ritz1, Chrystelle Guiter2,3, Flavia Castellano2,3, Karola Dorsch1, Julia Melzner1, Jean-Philippe Jais4,5, Gwendoline Dubois2,6, Philippe Gaulard2,3,6, Peter Möller1, and Karen Leroy2,3,6 1 Abteilung für Pathologie des Universitätklinikums Ulm, Ulm, Germany; 2 Inserm, Unité U955, Créteil, France; 3 Université Paris 12, Faculté de Médecine, Créteil, France; 4 Assistance Publique–Hôpitaux de Paris (AP-HP), Hôpital Necker, Service de Biostatistiques, Paris, France; 5 Université Paris Descartes, Paris, France; and 6 AP-HP, Groupe Hospitalier Henri-Mondor Albert-Chenevier, Département de Pathologie, Créteil, France Primary mediastinal B-cell lymphoma (PMBL) is a separate entity of aggressive B-cell lymphoma, characterized by a constitutive activation of janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling pathway, also observed in Hodgkin lymphoma. Although many cancers exhibit constitutive JAK-STAT pathway activation, mutations of STAT genes have not been reported in neoplasms. Here, we show that MedB-1 PMBL-derived and L1236 Hodgkin-derived cell lines and 20 of 55 (36%) PMBL cases harbor heterozygous missense mutations in STAT6 DNA binding domain, whereas no mutation was found in 25 diffuse large B-cell lymphoma samples. In 3 cases, somatic origin was indicated by the absence of the mutations in the nontumoral tissue. The pattern of STAT6 mutations was different from the classical features of somatic hypermutations. The mutant STAT6 proteins showed a decreased DNA binding ability in transfected HEK cells, but no decrease in expression of STAT6 canonical target genes was observed in PMBL cases with a mutated STAT6 gene. Although the oncogenic properties of STAT6 mutant proteins remain to be determined, their recurrent selection in PMBL strongly argues for their involvement in the pathogenesis of this aggressive B-cell lymphoma. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: STAT6 in PMBL: pathogenic or passenger? David A. Frank Blood 2009 114: 1133-1134. [Full Text] [PDF] This article has been cited by other articles: D. A. Frank STAT6 in PMBL: pathogenic or passenger? Blood, August 6, 2009; 114(6): 1133 - 1134. [Full Text] [PDF]

	Copyright © 2009 by American Society of Hematology         Online ISSN: 1528-0020