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Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma

Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors...

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Autores principales: Abate, Francesco, Ambrosio, Maria Raffaella, Mundo, Lucia, Laginestra, Maria Antonella, Fuligni, Fabio, Rossi, Maura, Zairis, Sakellarios, Gazaneo, Sara, De Falco, Giulia, Lazzi, Stefano, Bellan, Cristiana, Rocca, Bruno Jim, Amato, Teresa, Marasco, Elena, Etebari, Maryam, Ogwang, Martin, Calbi, Valeria, Ndede, Isaac, Patel, Kirtika, Chumba, David, Piccaluga, Pier Paolo, Pileri, Stefano, Leoncini, Lorenzo, Rabadan, Raul
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607508/
https://www.ncbi.nlm.nih.gov/pubmed/26468873
http://dx.doi.org/10.1371/journal.ppat.1005158
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author Abate, Francesco
Ambrosio, Maria Raffaella
Mundo, Lucia
Laginestra, Maria Antonella
Fuligni, Fabio
Rossi, Maura
Zairis, Sakellarios
Gazaneo, Sara
De Falco, Giulia
Lazzi, Stefano
Bellan, Cristiana
Rocca, Bruno Jim
Amato, Teresa
Marasco, Elena
Etebari, Maryam
Ogwang, Martin
Calbi, Valeria
Ndede, Isaac
Patel, Kirtika
Chumba, David
Piccaluga, Pier Paolo
Pileri, Stefano
Leoncini, Lorenzo
Rabadan, Raul
author_facet Abate, Francesco
Ambrosio, Maria Raffaella
Mundo, Lucia
Laginestra, Maria Antonella
Fuligni, Fabio
Rossi, Maura
Zairis, Sakellarios
Gazaneo, Sara
De Falco, Giulia
Lazzi, Stefano
Bellan, Cristiana
Rocca, Bruno Jim
Amato, Teresa
Marasco, Elena
Etebari, Maryam
Ogwang, Martin
Calbi, Valeria
Ndede, Isaac
Patel, Kirtika
Chumba, David
Piccaluga, Pier Paolo
Pileri, Stefano
Leoncini, Lorenzo
Rabadan, Raul
author_sort Abate, Francesco
collection PubMed
description Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively.
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spelling pubmed-46075082015-10-29 Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma Abate, Francesco Ambrosio, Maria Raffaella Mundo, Lucia Laginestra, Maria Antonella Fuligni, Fabio Rossi, Maura Zairis, Sakellarios Gazaneo, Sara De Falco, Giulia Lazzi, Stefano Bellan, Cristiana Rocca, Bruno Jim Amato, Teresa Marasco, Elena Etebari, Maryam Ogwang, Martin Calbi, Valeria Ndede, Isaac Patel, Kirtika Chumba, David Piccaluga, Pier Paolo Pileri, Stefano Leoncini, Lorenzo Rabadan, Raul PLoS Pathog Research Article Endemic Burkitt lymphoma (eBL) is primarily found in children in equatorial regions and represents the first historical example of a virus-associated human malignancy. Although Epstein-Barr virus (EBV) infection and MYC translocations are hallmarks of the disease, it is unclear whether other factors may contribute to its development. We performed RNA-Seq on 20 eBL cases from Uganda and showed that the mutational and viral landscape of eBL is more complex than previously reported. First, we found the presence of other herpesviridae family members in 8 cases (40%), in particular human herpesvirus 5 and human herpesvirus 8 and confirmed their presence by immunohistochemistry in the adjacent non-neoplastic tissue. Second, we identified a distinct latency program in EBV involving lytic genes in association with TCF3 activity. Third, by comparing the eBL mutational landscape with published data on sporadic Burkitt lymphoma (sBL), we detected lower frequencies of mutations in MYC, ID3, TCF3 and TP53, and a higher frequency of mutation in ARID1A in eBL samples. Recurrent mutations in two genes not previously associated with eBL were identified in 20% of tumors: RHOA and cyclin F (CCNF). We also observed that polyviral samples showed lower numbers of somatic mutations in common altered genes in comparison to sBL specimens, suggesting dual mechanisms of transformation, mutation versus virus driven in sBL and eBL respectively. Public Library of Science 2015-10-15 /pmc/articles/PMC4607508/ /pubmed/26468873 http://dx.doi.org/10.1371/journal.ppat.1005158 Text en © 2015 Abate et al http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Abate, Francesco
Ambrosio, Maria Raffaella
Mundo, Lucia
Laginestra, Maria Antonella
Fuligni, Fabio
Rossi, Maura
Zairis, Sakellarios
Gazaneo, Sara
De Falco, Giulia
Lazzi, Stefano
Bellan, Cristiana
Rocca, Bruno Jim
Amato, Teresa
Marasco, Elena
Etebari, Maryam
Ogwang, Martin
Calbi, Valeria
Ndede, Isaac
Patel, Kirtika
Chumba, David
Piccaluga, Pier Paolo
Pileri, Stefano
Leoncini, Lorenzo
Rabadan, Raul
Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title_full Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title_fullStr Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title_full_unstemmed Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title_short Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title_sort distinct viral and mutational spectrum of endemic burkitt lymphoma
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607508/
https://www.ncbi.nlm.nih.gov/pubmed/26468873
http://dx.doi.org/10.1371/journal.ppat.1005158
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