Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma.

Olga Ritz; Chrystelle Guiter; Flavia Castellano; Karola Dorsch; Julia Melzner; Jean-Philippe Jais; Gwendoline Dubois; Philippe Gaulard; Peter Möller; Karen Leroy

doi:10.1182/blood-2009-03-209759

Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma.: STAT6 mutations in mediastinal B-cell lymphoma

Olga Ritz ¹ Chrystelle Guiter ² Flavia Castellano ² Karola Dorsch ¹ Julia Melzner ¹ Jean-Philippe Jais ³ Gwendoline Dubois ^{2, 4} Philippe Gaulard ^{2, 4} Peter Möller ^{1, *} Karen Leroy ^{2, 4, *}

* Auteur correspondant

1 Abteilung für Pathologie

2 IMRB - Institut Mondor de Recherche Biomédicale

3 Service d'informatique médicale et biostatistiques [CHU Necker]

4 Département de pathologie [Mondor]

Abstract : 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.

Type de document :

Article dans une revue

Blood, American Society of Hematology, 2009, 114 (6), pp.1236-42. 〈10.1182/blood-2009-03-209759〉

Domaine :

Sciences du Vivant [q-bio] / Biochimie, Biologie Moléculaire

Liste complète des métadonnées

http://www.hal.inserm.fr/inserm-00411059
Contributeur : Georges Guellaen <>
Soumis le : mardi 25 août 2009 - 17:07:37
Dernière modification le : mardi 5 décembre 2017 - 17:06:01
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Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma.: STAT6 mutations in mediastinal B-cell lymphoma

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Recurrent mutations of the STAT6 DNA binding domain in primary mediastinal B-cell lymphoma.: STAT6 mutations in mediastinal B-cell lymphoma

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