Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality

ABSTRACT Epstein-Barr virus (EBV) is convincingly associated with gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. To test the hypothesis that there are additional cancer types with high prevalence of EBV, we determined EBV vi...

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Autores principales:	Sara R. Selitsky, David Marron, Lisle E. Mose, Joel S. Parker, Dirk P. Dittmer
Formato:	article
Lenguaje:	EN
Publicado:	American Society for Microbiology 2018
Materias:	B cells EBV Epstein-Barr virus TCGA virology cancer Microbiology QR1-502
Acceso en línea:	https://doaj.org/article/1c4cb053dfd34d19ab98808d4d76bf2a
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spelling	oai:doaj.org-article:1c4cb053dfd34d19ab98808d4d76bf2a2021-12-02T19:47:34ZEpstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality10.1128/mSystems.00081-182379-5077https://doaj.org/article/1c4cb053dfd34d19ab98808d4d76bf2a2018-10-01T00:00:00Zhttps://journals.asm.org/doi/10.1128/mSystems.00081-18https://doaj.org/toc/2379-5077ABSTRACT Epstein-Barr virus (EBV) is convincingly associated with gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. To test the hypothesis that there are additional cancer types with high prevalence of EBV, we determined EBV viral expression in all the Cancer Genome Atlas Project (TCGA) mRNA sequencing (mRNA-seq) samples (n = 10,396) from 32 different tumor types. We found that EBV was present in gastric adenocarcinoma and lymphoma, as expected, and was also present in >5% of samples in 10 additional tumor types. For most samples, EBV transcript levels were low, which suggests that EBV was likely present due to infected infiltrating B cells. In order to determine if there was a difference in the B-cell populations, we assembled B-cell receptors for each sample and found B-cell receptor abundance (P ≤ 1.4 × 10−20) and diversity (P ≤ 8.3 × 10−27) were significantly higher in EBV-positive samples. Moreover, diversity was independent of B-cell abundance, suggesting that the presence of EBV was associated with an increased and altered B-cell population. IMPORTANCE Around 20% of human cancers are associated with viruses. Epstein-Barr virus (EBV) contributes to gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. We assessed the prevalence of EBV in RNA-seq from 32 tumor types in the Cancer Genome Atlas Project (TCGA) and found EBV to be present in >5% of samples in 12 tumor types. EBV infects epithelial cells and B cells and in B cells causes proliferation. We hypothesized that the low expression of EBV in most of the tumor types was due to infiltration of B cells into the tumor. The increase in B-cell abundance and diversity in subjects where EBV was detected in the tumors strengthens this hypothesis. Overall, we found that EBV was associated with an increased and altered immune response. This result is not evidence of causality, but a potential novel biomarker for tumor immune status.Sara R. SelitskyDavid MarronLisle E. MoseJoel S. ParkerDirk P. DittmerAmerican Society for MicrobiologyarticleB cellsEBVEpstein-Barr virusTCGAvirologycancerMicrobiologyQR1-502ENmSystems, Vol 3, Iss 5 (2018)
institution	DOAJ
collection	DOAJ
language	EN
topic	B cells EBV Epstein-Barr virus TCGA virology cancer Microbiology QR1-502
spellingShingle	B cells EBV Epstein-Barr virus TCGA virology cancer Microbiology QR1-502 Sara R. Selitsky David Marron Lisle E. Mose Joel S. Parker Dirk P. Dittmer Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
description	ABSTRACT Epstein-Barr virus (EBV) is convincingly associated with gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. To test the hypothesis that there are additional cancer types with high prevalence of EBV, we determined EBV viral expression in all the Cancer Genome Atlas Project (TCGA) mRNA sequencing (mRNA-seq) samples (n = 10,396) from 32 different tumor types. We found that EBV was present in gastric adenocarcinoma and lymphoma, as expected, and was also present in >5% of samples in 10 additional tumor types. For most samples, EBV transcript levels were low, which suggests that EBV was likely present due to infected infiltrating B cells. In order to determine if there was a difference in the B-cell populations, we assembled B-cell receptors for each sample and found B-cell receptor abundance (P ≤ 1.4 × 10−20) and diversity (P ≤ 8.3 × 10−27) were significantly higher in EBV-positive samples. Moreover, diversity was independent of B-cell abundance, suggesting that the presence of EBV was associated with an increased and altered B-cell population. IMPORTANCE Around 20% of human cancers are associated with viruses. Epstein-Barr virus (EBV) contributes to gastric cancer, nasopharyngeal carcinoma, and certain lymphomas, but its role in other cancer types remains controversial. We assessed the prevalence of EBV in RNA-seq from 32 tumor types in the Cancer Genome Atlas Project (TCGA) and found EBV to be present in >5% of samples in 12 tumor types. EBV infects epithelial cells and B cells and in B cells causes proliferation. We hypothesized that the low expression of EBV in most of the tumor types was due to infiltration of B cells into the tumor. The increase in B-cell abundance and diversity in subjects where EBV was detected in the tumors strengthens this hypothesis. Overall, we found that EBV was associated with an increased and altered immune response. This result is not evidence of causality, but a potential novel biomarker for tumor immune status.
format	article
author	Sara R. Selitsky David Marron Lisle E. Mose Joel S. Parker Dirk P. Dittmer
author_facet	Sara R. Selitsky David Marron Lisle E. Mose Joel S. Parker Dirk P. Dittmer
author_sort	Sara R. Selitsky
title	Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
title_short	Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
title_full	Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
title_fullStr	Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
title_full_unstemmed	Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality
title_sort	epstein-barr virus-positive cancers show altered b-cell clonality
publisher	American Society for Microbiology
publishDate	2018
url	https://doaj.org/article/1c4cb053dfd34d19ab98808d4d76bf2a
work_keys_str_mv	AT sararselitsky epsteinbarrviruspositivecancersshowalteredbcellclonality AT davidmarron epsteinbarrviruspositivecancersshowalteredbcellclonality AT lisleemose epsteinbarrviruspositivecancersshowalteredbcellclonality AT joelsparker epsteinbarrviruspositivecancersshowalteredbcellclonality AT dirkpdittmer epsteinbarrviruspositivecancersshowalteredbcellclonality
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Epstein-Barr Virus-Positive Cancers Show Altered B-Cell Clonality

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