Various 30 and 69bp deletion variants of the Epstein-Barr virus LMP1 may arise by homologous recombination in nasopharyngeal carcinoma of Tunisian patients

Hadhri-Guiga, Boutheina; Khabir, Abdelmajid; Mokdad-Gargouri, Raja; Ghorbel, Abdelmonem; Drira, M.; Daoud, J.; Frikha, M.; Jlidi, R.; Gargouri, Ali

doi:10.1016/j.virusres.2005.07.002

Cited by 33 publications

(27 citation statements)

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“…5), which has not been previously described in the literature, leading to the loss of codons 345-371. Meanwhile, this unusual deletion strengthens and supports the model suggested by Hadri-Guiga et al [39]. In addition 30 or 81 bp deletions, the C terminus region of BNLF1 gene contained substitutions of amino acids compared with the B95-8 prototype and others published BNLF1 sequences from NPC strains (Fig.…”

Section: Discussionsupporting

confidence: 89%

Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma biopsies from Tunisian patients

et al. 2007

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Many studies suggest that the focal distribution of nasopharyngeal carcinoma (NPC) may be influenced not only by host genetics, diet and environments but also by interplay with Epstein-Barr virus (EBV) genetics. Specific EBV gene variants (the A and C types, the BamHI f configuration, a C terminal 30 bp deletion and a N terminal loss of an XhoI site in the BNLF1 gene) have been explored in high incidence areas in southern Asian NPC patients. In contrast, in Tunisia where NPC represents the most frequent type of Head and Neck cancer the distribution of these polymorphisms remains poorly investigated. In order to characterize the epidemiology of EBV variants in Tunisian NPC patients, we have investigated the A or B type of the EBV nuclear antigen (EBNA)2 gene, the C or D type of the BamHI W1/I1 region, the F/f variants of the BamHI F region and the presence or the absence of the XhoI site, 30 bp deletion and Taq1 site in the BNLF1 gene in 47 NPC biopsies, 12 being younger than 30 and 35 older than 30. Our results show a unique genetic profile of the tumor EBV strains regarding the A and D types, the prototype F and retention of the XhoI restriction site in the N terminal region of BNLF1 gene. With regard to the C terminal region of this gene, four genetic profiles were detected: (1) the occurrence of the 30 bp deletion in association with the Taq1 site in 39 cases (83%), (2) the presence of the Taq1 site by itself in 5 cases, (3) the occurrence of the 30 bp deletion by itself in 2 cases and (4) the occurrence of a new deletion of 81 bp covering the 30 bp deletion in association with the Taq1 site in one case. With the exception of the 81 bp deletion, which has not been previously described in the literature, the summarized results have shown the same genetic profile in Tunisian NPC tumor isolates as tumor isolates from other North African and Mediterranean countries. Hence, the observed EBV polymorphisms are not fully specific of to the Tunisian NPCs. Nevertheless, the notion of a divergence between North African and Asian tumor EBV isolates is reinforced by this study.

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Section: Discussionsupporting

confidence: 89%

Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma biopsies from Tunisian patients

et al. 2007

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“…Other types of sequence variation in the LMP1 carboxyl terminus-including the number of copies of a 33-bp repeat element, a 15-bp insertion in the third repeat element, and a 30-bp deletion in the carboxyl terminus-have repeatedly been detected in Chinese NPC tumors (119-121, 123, 124). The 30-bp deletion, detected also in a proportion of Alaska native, Caucasian (125,126), Malaysian (122), and North African NPC (127,128), seems to enhance the transforming potential of LMP1 in vitro, and may be present in more aggressive disease forms (117,(129)(130)(131). However, there is no strong evidence that the deleted variant is associated with increased risk of NPC (120,123,132,133), and there is a lack of large, well-designed epidemiologic studies of risk associations with EBV variants.…”

Section: Risk Factorsmentioning

confidence: 93%

The Enigmatic Epidemiology of Nasopharyngeal Carcinoma

Chang

Adami

2006

Cancer Epidemiology, Biomarkers &Amp; Prevention

1,161

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Nasopharyngeal carcinoma (NPC) has a unique and complex etiology that is not completely understood. Although NPC is rare in most populations, it is a leading form of cancer in a few well-defined populations, including natives of southern China, Southeast Asia, the Arctic, and the Middle East/North Africa. The distinctive racial/ethnic and geographic distribution of NPC worldwide suggests that both environmental factors and genetic traits contribute to its development. This review aims to summarize the current knowledge regarding the epidemiology of NPC and to propose new avenues of research that could help illuminate the causes and ultimately the prevention of this remarkable disease. Well-established risk factors for NPC include elevated antibody titers against the Epstein-Barr virus, consumption of salt-preserved fish, a family history of NPC, and certain human leukocyte antigen class I genotypes. Consumption of other preserved foods, tobacco smoking, and a history of chronic respiratory tract conditions may be associated with elevated NPC risk, whereas consumption of fresh fruits and vegetables and other human leukocyte antigen genotypes may be associated with decreased risk. Evidence for a causal role of various inhalants, herbal medicines, and occupational exposures is inconsistent. Other than dietary modification, no concrete preventive measures for NPC exist. Given the unresolved gaps in understanding of NPC, there is a clear need for large-scale, populationbased molecular epidemiologic studies to elucidate how environmental, viral, and genetic factors interact in both the development and the prevention of this disease. PurposeIntriguing hallmarks of nasopharyngeal carcinoma (NPC) include its striking racial/ethnic and geographic variation, as well as its multifactorial etiology involving the interplay of environmental, viral, and genetic risk factors. The precise roles of these factors in the development of NPC, however, remain unknown. The purpose of this review is to highlight what is understood about the epidemiology of NPC, as well as to present unresolved research questions that call for large-scale molecular epidemiologic studies of NPC to illuminate the underlying causes of this fascinating disease. Review MethodsA thorough review of the literature related to the etiology of NPC was undertaken, starting with a Medline search from 1966 onward. Additional papers, book sections, and monographs were identified through examination of reference lists. Because this review aims to present the epidemiologic evidence in a range of topic areas, rather than to calculate overall estimates of effect, formal quantitative methods were not used. All relevant papers have been cited to provide a comprehensive summary of the evidence. Inclusion or exclusion criteria were not applied to individual reports, but the strength, consistency, and relevance of the findings were considered in weighing the evidence.Descriptive Epidemiology

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“…Both this variant, and the more common 30-bp deletion mutant, were found more frequently in the NPC biopsies when compared with either future science group normal nasopharyngeal tissue or peripheral blood from the same patients, suggesting that these deletions were indeed associated with the tumorigenic process [126]. Another LMP1 variant, 2117-LMP1, is prevalent in Hong Kong and has been demonstrated to induce proliferation and provides resistance to apoptosis induced by growth factor depletion in NP69 cells [43].…”

Section: Lmp1 Strain Variants and Npcmentioning

confidence: 93%

Role of The Epstein–Barr Virus-Encoded Latent Membrane Protein-1, LMP1, in The Pathogenesis of Nasopharyngeal Carcinoma

2009

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Although frequently expressed in Epstein-Barr virus (EBV)-positive malignancies, the contribution of the oncogenic latent membrane protein-1 (LMP1) to the pathogenesis of nasopharyngeal carcinoma remains to be fully defined. As a key effector in EBV-driven B-cell transformation in vitro, LMP1 also displays oncogenic properties in rodent fibroblasts, and exhibits similar effects in epithelial cells. LMP1 functions as a viral mimic of the TNFR family member, CD40, engaging a plethora of signaling pathways including: NF-kappaB, JNK/p38 (SAPK), PI3-kinase and ERK-MPK. The constitutive activation of these pathways appears central in the ability of LMP1 to induce multiple morphological and phenotypic alterations. Here we review the effects of LMP1 on epithelial cell growth transformation, and its putative role in the pathogenesis of nasopharyngeal carcinoma, focusing on key areas of proliferation, survival, cell motility and invasion.

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Various 30 and 69bp deletion variants of the Epstein-Barr virus LMP1 may arise by homologous recombination in nasopharyngeal carcinoma of Tunisian patients

Cited by 33 publications

References 20 publications

Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma biopsies from Tunisian patients

Polymorphism analysis of Epstein-Barr virus isolates of nasopharyngeal carcinoma biopsies from Tunisian patients

The Enigmatic Epidemiology of Nasopharyngeal Carcinoma

Role of The Epstein–Barr Virus-Encoded Latent Membrane Protein-1, LMP1, in The Pathogenesis of Nasopharyngeal Carcinoma

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