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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Main Authors:	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
Format:	Online
Language:	English
Published:	Public Library of Science 2015
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607508/

id	pubmed-4607508
recordtype	oai_dc
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 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.
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
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
spellingShingle	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
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
title	Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma
title_short	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_sort	distinct viral and mutational spectrum of endemic burkitt lymphoma
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.
publisher	Public Library of Science
publishDate	2015
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4607508/
_version_	1613488816009510912

Distinct Viral and Mutational Spectrum of Endemic Burkitt Lymphoma

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