The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas–Another Model of Disrupted Human-Pathogen Co-Evolution

Corvalán, Alejandro; Ruedlinger, Jenny; Mayo, Tomas de; Polakovičová, Iva; González‐Hormazábal, Patricio; Aguayo, Francisco

doi:10.3390/cancers11020217

Cited by 8 publications

(7 citation statements)

References 115 publications

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“…Several EBV-related cancers exhibit a distinct geographyspecific distribution (elaborated elsewhere in this review) and some of these distributions have been attributed to phylogeographical variations between different EBV strains (Jemal et al 2011;Corvalan et al 2019). Early attempts to classify these differences led to the discovery of EBV Types 1 and 2 (or A and B) based on differences in genetic sequences (Zimber et al 1986;Chang et al 2009).…”

Section: Introductionmentioning

confidence: 97%

Estimating the global burden of Epstein–Barr virus-related cancers

Wong

Meehan

Burrows

et al. 2021

J Cancer Res Clin Oncol

116

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Background More than 90% of the adult population globally is chronically infected by the Epstein–Barr virus (EBV). It is well established that EBV is associated with a number of malignancies, and advances in knowledge of EBV-related malignancies are being made every year. Several studies have analysed the global epidemiology and geographic distribution of EBV-related cancers. However, most have only described a single cancer type or subtype in isolation or limited their study to the three or four most common EBV-related cancers. This review will present an overview on the spectrum of cancers linked to EBV based on observations of associations and proportions in the published literature while also using these observations to estimate the incidence and mortality burden of some of these cancers. Method We have reviewed the literature on defining features, distribution and outcomes across six cancers with a relatively large EBV-related case burden: Nasopharyngeal carcinoma (NPC), Gastric carcinoma (GC), Hodgkin lymphoma (HL), Burkitt lymphoma (BL), Diffuse large B-cell lymphoma (DLBCL) and Extranodal NK/T-cell lymphoma, Nasal type (ENKTL-NT). We retrieved published region-specific EBV-related case proportions for NPC, GC, HL and BL and performed meta-analyses on pooled region-specific studies of EBV-related case proportions for DLBCL and ENKTL-NT. We match these pooled proportions with their respective regional incidence and mortality numbers retrieved from a publicly available cancer database. Additionally, we also reviewed the literature on several other less common EBV-related cancers to summarize their key characteristics herein. Conclusion We estimated that EBV-related cases from these six cancers accounted for 239,700–357,900 new cases and 137,900–208,700 deaths in 2020. This review highlights the significant global impact of EBV-related cancers and extends the spectrum of disease that could benefit from an EBV-specific therapeutic.

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Section: Introductionmentioning

confidence: 97%

Estimating the global burden of Epstein–Barr virus-related cancers

Wong

Meehan

Burrows

et al. 2021

J Cancer Res Clin Oncol

116

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“…As occurs with GC incidence, the distribution of histological types and the frequency of both H. pylori and EBV are highly heterogeneous across the globe. In Chile, >70% of the population is H. pylori + [8], while approximately a 16% of GCs are EBV+ [9,10], a percentage much higher than the observed in most countries [9,11,12].…”

Section: Introductionmentioning

confidence: 99%

High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study

Córdova-Delgado

Pinto

Retamal

et al. 2019

Cancers

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Gastric cancer (GC) is a heterogeneous disease. This heterogeneity applies not only to morphological and phenotypic features but also to geographical variations in incidence and mortality rates. As Chile has one of the highest mortality rates within South America, we sought to define a molecular profile of Chilean GCs (ClinicalTrials.gov identifier: NCT03158571/(FORCE1)). Solid tumor samples and clinical data were obtained from 224 patients, with subsets analyzed by tissue microarray (TMA; n = 90) and next generation sequencing (NGS; n = 101). Most demographic and clinical data were in line with previous reports. TMA data indicated that 60% of patients displayed potentially actionable alterations. Furthermore, 20.5% were categorized as having a high tumor mutational burden, and 13% possessed micro-satellite instability (MSI). Results also confirmed previous studies reporting high Epstein-Barr virus (EBV) positivity (13%) in Chilean-derived GC samples suggesting a high proportion of patients could benefit from immunotherapy. As expected, TP53 and PIK3CA were the most frequently altered genes. However, NGS demonstrated the presence of TP53, NRAS, and BRAF variants previously unreported in current GC databases. Finally, using the Kendall method, we report a significant correlation between EBV+ status and programmed death ligand-1 (PDL1)+ and an inverse correlation between p53 mutational status and MSI. Our results suggest that in this Chilean cohort, a high proportion of patients are potential candidates for immunotherapy treatment. To the best of our knowledge, this study is the first in South America to assess the prevalence of actionable targets and to examine a molecular profile of GC patients.

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“…The ORFs encode proteins involved in regulation of DNA replication and gene expression, and maintenance of genome integrity in daughter cells [18]. The nomenclatures of the ORFs were determined based on the Bam HI restriction fraction map in which the genes were in decreasing order according to their sizes [19]. The protein coding genes are divided into lytic and latent genes which play structural and non-structural roles.…”

Section: Genome Structure Of Ebvmentioning

confidence: 99%

Epstein Barr Virus Associated Lymphomas and Epithelia Cancers in Humans

Ayee¹,

Ofori²,

Wright³

et al. 2020

J. Cancer

108

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Epstein Barr virus (EBV) is a cosmopolitan oncogenic virus, infecting about 90% of the world's population and it is associated to tumors originating from both epithelia and hematopoietic cells. Transmission of the virus is mainly through oral secretions; however, transmission through organ transplantation and blood transfusion has been reported. In order to evade immune recognition, EBV establishes latent infection in B lymphocytes where it expresses limited sets of proteins called EBV transcription programs (ETPs), including six nuclear antigens (EBNAs), three latent membrane proteins (LMP), and untranslated RNA called EBV encoded RNA (EBER), shown to efficiently transform B cells into lymphoblastic cells. These programs undergo different patterns of expression which determine the occurrence of distinct types of latency in the pathogenesis of a particular tumor. Hematopoietic cell derived tumors include but not limited to Burkitt's lymphoma, Hodgkin lymphoma, post-transplant lymphoproliferative disorders, and natural killer (NK)/T cell lymphoma. EBV undergoes lytic infection in epithelia cells for amplification of the viral particle for transmission where it expresses lytic stage genes. However, for reasons yet to be unveiled, EBV switches from the expression of lytic stage genes to the expression of ETPs in epithelia cells. The expression of the ETPs lead to the transformation of epithelia cells into permanently proliferating cells, resulting in epithelia cell derived malignancies such as nasopharyngeal cancer, gastric cancer, and breast cancer. In this review, we have summarized the current updates on EBV associated epithelial and B cell-derived malignancies, and the role of EBV latency gene products in the pathogenesis of the cancers, and have suggested areas for future studies when considering therapeutic measures

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The Phylogeographic Diversity of EBV and Admixed Ancestry in the Americas–Another Model of Disrupted Human-Pathogen Co-Evolution

Cited by 8 publications

References 115 publications

Estimating the global burden of Epstein–Barr virus-related cancers

Estimating the global burden of Epstein–Barr virus-related cancers

High Proportion of Potential Candidates for Immunotherapy in a Chilean Cohort of Gastric Cancer Patients: Results of the FORCE1 Study

Epstein Barr Virus Associated Lymphomas and Epithelia Cancers in Humans

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