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Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma

Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on th...

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Autores principales: Amato, Teresa, Abate, Francesco, Piccaluga, Pierpaolo, Iacono, Michele, Fallerini, Chiara, Renieri, Alessandra, De Falco, Giulia, Ambrosio, Maria Raffaella, Mourmouras, Vaselious, Ogwang, Martin, Calbi, Valeria, Rabadan, Roul, Hummel, Michael, Pileri, Stefano, Leoncini, Lorenzo, Bellan, Cristiana
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2016
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778259/
https://www.ncbi.nlm.nih.gov/pubmed/26712879
http://dx.doi.org/10.1093/ajcp/aqv011
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author Amato, Teresa
Abate, Francesco
Piccaluga, Pierpaolo
Iacono, Michele
Fallerini, Chiara
Renieri, Alessandra
De Falco, Giulia
Ambrosio, Maria Raffaella
Mourmouras, Vaselious
Ogwang, Martin
Calbi, Valeria
Rabadan, Roul
Hummel, Michael
Pileri, Stefano
Leoncini, Lorenzo
Bellan, Cristiana
author_facet Amato, Teresa
Abate, Francesco
Piccaluga, Pierpaolo
Iacono, Michele
Fallerini, Chiara
Renieri, Alessandra
De Falco, Giulia
Ambrosio, Maria Raffaella
Mourmouras, Vaselious
Ogwang, Martin
Calbi, Valeria
Rabadan, Roul
Hummel, Michael
Pileri, Stefano
Leoncini, Lorenzo
Bellan, Cristiana
author_sort Amato, Teresa
collection PubMed
description Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development.
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spelling pubmed-47782592016-07-14 Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma Amato, Teresa Abate, Francesco Piccaluga, Pierpaolo Iacono, Michele Fallerini, Chiara Renieri, Alessandra De Falco, Giulia Ambrosio, Maria Raffaella Mourmouras, Vaselious Ogwang, Martin Calbi, Valeria Rabadan, Roul Hummel, Michael Pileri, Stefano Leoncini, Lorenzo Bellan, Cristiana Am J Clin Pathol Original Articles Objectives: Recent studies using next-generation sequencing (NGS) analysis disclosed the importance of the intrinsic activation of the B-cell receptor (BCR) pathway in the pathogenesis of sporadic Burkitt lymphoma (sBL) due to mutations of TCF3/ID3 genes. Since no definitive data are available on the genetic landscape of endemic Burkitt (eBL), we first assessed the mutation frequency of TCF3/ID3 in eBL compared with sBL and subsequently the somatic hypermutation status of the BCR to answer whether an extrinsic activation of BCR signaling could also be demonstrated in Burkitt lymphoma. Methods: We assessed the mutations of TCF3/ID3 by RNAseq and the BCR status by NGS analysis of the immunoglobulin genes (IGs). Results: We detected mutations of TCF3/ID3 in about 30% of the eBL cases. This rate is significantly lower than that detected in sBL (64%). The NGS analysis of IGs revealed intraclonal diversity, suggesting an active targeted somatic hypermutation process in eBL compared with sBL. Conclusions: These findings support the view that the antigenic pressure plays a key role in the pathogenetic pathways of eBL, which may be partially distinct from those driving sBL development. Oxford University Press 2016-01 2015-12-23 /pmc/articles/PMC4778259/ /pubmed/26712879 http://dx.doi.org/10.1093/ajcp/aqv011 Text en © American Society for Clinical Pathology, 2016. http://creativecommons.org/licenses/by-nc/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits non-commercial re-use, distribution, and reproduction in any medium, provided the original work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Original Articles
Amato, Teresa
Abate, Francesco
Piccaluga, Pierpaolo
Iacono, Michele
Fallerini, Chiara
Renieri, Alessandra
De Falco, Giulia
Ambrosio, Maria Raffaella
Mourmouras, Vaselious
Ogwang, Martin
Calbi, Valeria
Rabadan, Roul
Hummel, Michael
Pileri, Stefano
Leoncini, Lorenzo
Bellan, Cristiana
Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma
title Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma
title_full Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma
title_fullStr Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma
title_full_unstemmed Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma
title_short Clonality Analysis of Immunoglobulin Gene Rearrangement by Next-Generation Sequencing in Endemic Burkitt Lymphoma Suggests Antigen Drive Activation of BCR as Opposed to Sporadic Burkitt Lymphoma
title_sort clonality analysis of immunoglobulin gene rearrangement by next-generation sequencing in endemic burkitt lymphoma suggests antigen drive activation of bcr as opposed to sporadic burkitt lymphoma
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4778259/
https://www.ncbi.nlm.nih.gov/pubmed/26712879
http://dx.doi.org/10.1093/ajcp/aqv011
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