TSitologiya i Genetika 2022, vol. 56, no. 6, 81-82
Cytology and Genetics 2022, vol. 56, no. 6, 559–566, doi: https://www.doi.org/10.3103/S0095452722060068

BARR Novel genetic variant of 30­bp deletion: a polymorphism of latent membrane protein 1 from vietnamese epstein virus­associated nasopharyngeal carcinoma biopsies

Lao T.D., Le T.A.H.

  • Department of Pharmaceutical and Medical Biotechnology, Faculty of Biotechnology, Ho Chi Minh City Open University, Ho Chi Minh City, 700000, Vietnam

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.

Keywords: 30-bp deletion, LMP-1, nasopharyngeal carcinoma, polymorphism, C-cytoplasmic

TSitologiya i Genetika
2022, vol. 56, no. 6, 81-82

Current Issue
Cytology and Genetics
2022, vol. 56, no. 6, 559–566,
doi: 10.3103/S0095452722060068

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References

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

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

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

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

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

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

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

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.

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.

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.

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.

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

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

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

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

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

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

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

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.

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

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