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Novel Genetic Variant of 30-bp Deletion: A Polymorphism of Latent Membrane Protein 1 from Vietnamese Epstein Barr Virus-Associated Nasopharyngeal Carcinoma Biopsies

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Abstract

Nasopharyngeal carcinoma (NPC) is the most common cancer of in the areas of head and neck cancer, which gravitates toward Asia. NPC is tightly associated with the gene expression of Epstein Barr Virus (EBV). Among them, Latent membrane protein 1 (LMP-1) gene, and its 30-bp deleted variant have profound effects on many pathways of NPC pathogenesis leading to the tumorigenesis. The study of the 30-bp deleted variant was not performed in Vietnam, the high endemic NPC country. Therefore, the aim of the current study is to analyze the genetic characteristics of whether present a 30-bp deletion in NPC biopsy tumors is associated with EBV. Twenty biopsy NPC samples were collected from local patients, analyzed by PCR-sequencing and compared to the prototype B95-8 30-bp deletion variant. As the results, the 30-bp deletion polymorphism was recorded in 55.00% samples. The 30-bp deletion polymorphism yielded from nucleotide 168 285 to nucleotide 168 256, different from the prototype B95-8 and other previously reported sequences. Therefore, we termed as the new 30-bp deletion* observed in the region of CDS LMP-1 gene. Three patterns of amino acid substitution/deletion observed in 30-bp deletion/no 30-bp deletion in LMP-1 C-cytoplasmic terminus were recorded. In conclusion, the new 30-bp deletion* variant, which was different from previously reported 30-bp deletion, as well as the pattern of amino acid substitution/deletion was investigated in the Vietnamese nasopharyngeal carcinoma biopsy samples.

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REFERENCES

  1. Chen, Y.P., Chan, A.T.C., Le, Q.T., et al., Nasopharyngeal carcinoma, Lancet, 2019, vol. 394, pp. 64–80.

    Article  PubMed  Google Scholar 

  2. Cheung, S.T., Leung, S.F., Lo, K.W., et al., Specific latent membrane protein 1 gene sequences in type 1 and type 2 Epstein-Barr virus from nasopharyngeal carcinoma in Hong Kong, Int. J. Cancer, 1998, vol. 76, pp. 399–406. https://doi.org/10.1002/(sici)1097-0215(19980504)76:3<399::aid-ijc18>3.0.co;2-6

    Article  CAS  PubMed  Google Scholar 

  3. da Costa, V.G., Marques-Silva, A.C., and Moreli, M.L., The Epstein-Barr virus latent membrane protein-1 (LMP1) 30-bp deletion and XhoI-polymorphism in nasopharyngeal carcinoma: a meta-analysis of observational studies, Syst. Rev., 2015, vol. 4, p. 46. https://doi.org/10.1186/s13643-015-0037-z

    Article  PubMed  PubMed Central  Google Scholar 

  4. Eliopoulos, A.G. and Young, L.S., LMP1 structure and signal transduction, Semin. Cancer Biol., 2001, vol. 11, pp. 435–444. https://doi.org/10.1006/scbi.2001.0410

    Article  CAS  PubMed  Google Scholar 

  5. Hadhri-Guiga, B., Khabir, A.M., Mokdad-Gargouri, R., et al., Various 30 and 69 bp deletion variants of the Epstein-Barr virus LMP1 may arise by homologous recombination in nasopharyngeal carcinoma of Tunisian patients, Virus Res., 2006, vol. 115, pp. 24–30. https://doi.org/10.1016/j.virusres.2005.07.002

    Article  CAS  PubMed  Google Scholar 

  6. Hahn, P., Novikova, E., Scherback, L., et al., The LMP1 gene isolated from Russian nasopharyngeal carcinoma has no 30-bp deletion, Int. J. Cancer, 2001, vol. 91, pp. 815–821. https://doi.org/10.1002/1097-0215(200002)9999:9999<::aid-ijc1122>3.0.co;2-w

    Article  CAS  PubMed  Google Scholar 

  7. Kim, L.H., Peh, S.C., and Poppema, S., Dual variant of Epstein-Barr virus in Hodgkin/Reed-Sternberg cells: Single-cell PCR study on latent membrane protein-1 gene, Int. J. Cancer, 2003, vol. 107, pp. 250–255. https://doi.org/10.1002/ijc.11395

    Article  CAS  PubMed  Google Scholar 

  8. Knecht, H., Bachmann, E., Brousset, P., et al., Deletions within the LMP1 oncogene of Epstein-Barr virus are clustered in Hodgkin’s disease and identical to those observed in nasopharyngeal carcinoma, Blood, 1993, vol. 82, no. 10, pp. 2937–2942.

    Article  CAS  PubMed  Google Scholar 

  9. Lao, D.T. and Le, T.A.H., Epidemiology, incidence and mortality of nasopharynx cancer in Southeast Asia: an update report, Adv. Life Sci., 2020, vol. 7, pp. 86–90.

    Google Scholar 

  10. Li, S., Chang, Y., and Liu, S., Effect of a 10-amino acid deletion on the oncogenic activity of latent membrane protein 1 of Epstein-Barr virus, Oncogene, 1996, vol. 12, pp. 2129–2135.

    CAS  PubMed  Google Scholar 

  11. Nurhantari, Y., Emoto, N., Rahayu, P., et al., Nasopharyngeal carcinoma in Indonesia has a low prevalence of the 30-base pair deletion of Epstein-Barr virus latent membrane protein 1, Southeast Asian J. Trop. Med. Public Health, 2003, vol. 34, pp. 98–105.

    CAS  PubMed  Google Scholar 

  12. Pathmanathan, R., Prasad, U., Sadler, R., et al., Clonal proliferations of cells infected with Epstein–Barr virus in preinvasive lesions related to nasopharyngeal carcinoma, N. Engl. J. Med., 1995, vol. 333, pp. 693–698. https://doi.org/10.1056/NEJM199509143331103

    Article  CAS  PubMed  Google Scholar 

  13. Raab-Traub, N., Epstein-Barr virus in the pathogenesis of NPC, Semin. Cancer Biol., 2002, vol. 12, no. 6, pp. 431–441. https://doi.org/10.1016/s1044579x0200086x

    Article  CAS  PubMed  Google Scholar 

  14. Rowe, D.T., Epstein-Barr virus immortalization and latency, Front. Biosci., 1999, vol. 4, no. 4, pp. 346–371. https://doi.org/10.2741/rowe

    Article  Google Scholar 

  15. See, H., Yap, Y., Yip, W., et al., Epstein-Barr virus latent membrane protein-1 (LMP-1) 30-bp deletion and Xho I-loss is associated with type III nasopharyngeal carcinoma in Malaysia, World J. Surg. Oncol., 2008, vol. 6, p. 18. https://doi.org/10.1186/1477-7819-6-18

    Article  PubMed  PubMed Central  Google Scholar 

  16. Senyuta, N., Yakovleva, L., Goncharova, E., et al., Epstein-Barr virus latent membrane protein 1 polymorphism in nasopharyngeal carcinoma and other oral cavity tumors in Russia, J. Med. Virol., 2014, vol. 86, no. 2, pp. 290–300. https://doi.org/10.1002/jmv.23729

    Article  CAS  PubMed  Google Scholar 

  17. Shair, K.H.Y., Reddy, A., and Cooper, V.S., New insights from elucidating the role of LMP1 in nasopharyngeal carcinoma, Cancers (Basel), 2018, vol. 10, no. 4, p. 86. https://doi.org/10.3390/cancers10040086

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Tang, Y.L., Lu, J.H., Cao, L., et al., Genetic variations of EBV-LMP1 from nasopharyngeal carcinoma biopsies: potential loss of T cell epitopes, Braz. J. Med. Biol. Res., 2008, vol. 41, no. 2, pp. 110–116. https://doi.org/10.1590/s0100-879x2008000200006

    Article  CAS  PubMed  Google Scholar 

  19. Tao, Q., Ambinder, R., and Swinnen, L., Epstein-Barr virus (EBV) variant with a 30-bp deletion at the carboxyl terminus (amino acids 346-355) of latent membrane protein-1 (LMP1) gene is able to transform cells and evade immune surveillance, Am. J. Pathol., 1998, vol. 152, no. 5, pp. 1398–1399.

    CAS  PubMed  PubMed Central  Google Scholar 

  20. Zhang, X.S., Song, K.H., Mai, H.Q., et al., The 30-bp deletion variant: a polymorphism of latent membrane protein 1 prevalent in endemic and non-endemic areas of nasopharyngeal carcinomas in China, Cancer Lett., 2002, vol. 176, pp. 65–73. https://doi.org/10.1016/s0304-3835(01)00733-9

    Article  CAS  PubMed  Google Scholar 

  21. Zhang, Z., Yu, X., Zhou, Z., et al., LMP1-positive extracellular vesicles promote radioresistance in nasopharyngeal carcinoma cells through P38 MAPK signaling, Cancer Med., 2019, vol. 8, pp. 6082–6094. https://doi.org/10.1002/cam4.2506

    Article  CAS  PubMed  PubMed Central  Google Scholar 

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ACKNOWLEDGMENTS

We wish to express our thanks to the research project sponsored by Ho Chi Minh City Open University, Ho Chi Minh City, Vietnam. We wish to express our thanks for the research project sponsored by the Ministry of Education and Training, Vietnam; Ho Chi Minh City Open University; We also thank all the recruited participants in this work and Dr. Nguyen Trong Minh, Dr. Nguyen Huu Dung, all the otorhinolaryngology staff members of in Cho Ray Hospital, Ho Chi Minh City, for collecting the samples used in these studies. We are thankful to the participants in our study and appreciated the contributions of the staffs from Molecular Biology Laboratory, Ho Chi Minh City Open University.

Funding

This research received funding sponsored by Ho Chi Minh City Open University, Ho Chi Minh City, Vietnam under the grant number E2018.3.1.

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Contributions

Study design: Lao T.D., Le T.A.H.; Experiment performance, data acquisition, writing and editing of the manuscript. All authors reviewed and approved the final version of the manuscript.

Corresponding authors

Correspondence to Thuan Duc Lao or Thuy Ai Huyen Le.

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Conflict of interest. The authors declare that they have no conflicts of interest.

Statement of compliance with standards of research involving humans as subjects. Institutional Ethics Board approval was obtained from the Medical Ethics Committee of the Cho Ray Hospital, Ho Chi Minh City, Vietnam (the decision number of the permission: 516/BVCR-HDDD). The patients enrolled in this study were required to sign consent forms to approve the usage of the samples for laboratory work and analysis.

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Lao, T.D., Le, T.A. Novel Genetic Variant of 30-bp Deletion: A Polymorphism of Latent Membrane Protein 1 from Vietnamese Epstein Barr Virus-Associated Nasopharyngeal Carcinoma Biopsies. Cytol. Genet. 56, 559–566 (2022). https://doi.org/10.3103/S0095452722060068

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  • DOI: https://doi.org/10.3103/S0095452722060068

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