A capture-sequencing strategy identifies IRF8, EBF1, and APRIL as novel IGH fusion partners in B-cell lymphoma.
Blood
; 122(5): 726-33, 2013 Aug 01.
Article
en En
| MEDLINE
| ID: mdl-23775715
ABSTRACT
The characterization of immunoglobulin heavy chain (IGH) translocations provides information on the diagnosis and guides therapeutic decisions in mature B-cell malignancies while enhancing our understanding of normal and malignant B-cell biology. However, existing methodologies for the detection of IGH translocations are labor intensive, often require viable cells, and are biased toward known IGH fusions. To overcome these limitations, we developed a capture sequencing strategy for the identification of IGH rearrangements at nucleotide level resolution and tested its capabilities as a diagnostic and discovery tool in 78 primary diffuse large B-cell lymphomas (DLBCLs). We readily identified IGH-BCL2, IGH-BCL6, IGH-MYC, and IGH-CCND1 fusions and discovered IRF8, EBF1, and TNFSF13 (APRIL) as novel IGH partners in these tumors. IRF8 and TNFSF13 expression was significantly higher in lymphomas with IGH rearrangements targeting these loci. Modeling the deregulation of IRF8 and EBF1 in vitro defined a lymphomagenic profile characterized by up-regulation of AID and/or BCL6, down-regulation of PRMD1, and resistance to apoptosis. Using a capture sequencing strategy, we discovered the B-cell relevant genes IRF8, EBF1, and TNFSF13 as novel targets for IGH deregulation. This methodology is poised to change how IGH translocations are identified in clinical settings while remaining a powerful tool to uncover the pathogenesis of B-cell malignancies.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas de Fusión Oncogénica
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Transactivadores
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Linfoma de Células B
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Cadenas Pesadas de Inmunoglobulina
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Factores Reguladores del Interferón
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Miembro 13 de la Superfamilia de Ligandos de Factores de Necrosis Tumoral
Tipo de estudio:
Prognostic_studies
Límite:
Humans
Idioma:
En
Revista:
Blood
Año:
2013
Tipo del documento:
Article
País de afiliación:
Estados Unidos