Iranian Journal of Pathology

TERT Promoter Mutation in Benign and Malignant Salivary Gland Tumors; A Cross-Sectional Study

Document Type : Original Research

Authors

Ali Zare-Mirzaie 1
Shamim Mollazadehghomi 2
Seyed Mohammad Heshmati 1
Amirhosein Mehrtash 3
Shabnam Mollazadehghomi 1

1 Department of Pathology, School of Medicine, Iran University of Medical Sciences, Tehran, Iran

2 Cellular and Molecular Research Center, Research Institute for Non-Communicable Diseases, Qazvin University of Medical Sciences, Qazvin, Iran

3 Molecular Medicine Department, Biotechnology Research Center, Pasteur Institute of Iran, Tehran, Iran

https://doi.org/10.30699/ijp.2023.556651.2927
Abstract
Background & Objective: Telomere-related tumorigenesis mechanisms in the salivary gland, including mutation in the promoter region of TERT, have been rarely investigated. Therefore, the present study aimed to investigate the mutation in the promoter region of TERT in benign and malignant salivary gland tumors.
Methods: This was a descriptive-analytical cross-sectional study. Tissue samples of 54 patients with primary salivary gland tumors sent to the pathology department of Rasool-e-Akram Hospital from September 2017 to September 2021 were examined. Fifteen samples including two groups of the most common benign tumors (n=5; 3 pleomorphic adenomas and 2 Warthin tumors) and four groups of the most common malignant tumors (n=10; 3 mucoepidermoid carcinomas, 3 adenoid cystic carcinomas, 2 acinic cell carcinoma, and 2 salivary duct carcinoma) were selected. The promoter region of TERT, including well-known hot spot regions, is sequenced using the Sanger sequencing method. Data were analyzed using statistical software R version 4.1.2.
Results: Of 15 salivary gland tumor specimens, consisting of  5 benign tumors and 10 malignant tumors after DNA sequencing, TERT promoter region mutation was only seen in one of the adenoid cystic carcinoma samples, located at -146 bp upstream from ATG (chr5: 1,295,250 C>T).
Conclusion: TERT promoter mutation was not different in malignant and benign salivary tumors. Nonetheless, there are a few studies that report TERT promoter mutation in adenoid cystic carcinoma of the salivary gland, necessitating the need for further investigations.

Keywords

DNA sequencing
Salivary gland tumors
TERT promoter mutation

Subjects

  1. Mehta D, Willging JP, editors. Pediatric salivary gland lesions. Seminars in pediatric surgery; 2006: Elsevier. [PMID] [DOI:10.1053/j.sempedsurg.2006.02.004]
  2. Bernstein JM. Mucosal immunology of the upper respiratory tract. Respiration. 1992;59 Suppl 3(Suppl. 3):3-13. [DOI:10.1159/000196123] [PMID]
  3. Fitzpatrick SG, Cohen DM, Clark AN. Ulcerated Lesions of the Oral Mucosa: Clinical and Histologic Review. Head Neck Pathol. 2019;13(1):91-102. [DOI:10.1007/s12105-018-0981-8] [PMID] [PMCID]
  4. Scognamiglio T. Head and Neck Pathology. Frozen Section Pathology: Springer; 2021. p. 101-26. [DOI:10.1007/978-3-030-71308-9_5]
  5. Peraza A, Gomez R, Beltran J, Amarista FJ. Mucoepidermoid carcinoma. An update and review of the literature. J Stomatol Oral Maxillofac Surg. 2020;121(6):713-20. [DOI:10.1016/j.jormas.2020.06.003] [PMID]
  6. Wang H, Weiss VL, Hoffman RD, Abel T, Ho RH, Borinstein SC, et al. Salivary Gland NUT Carcinoma with Prolonged Survival in Children: Case Illustration and Systematic Review of Literature. Head Neck Pathol. 2021;15(1):236-43. [DOI:10.1007/s12105-020-01141-3] [PMID] [PMCID]
  7. Almeslet AS. Pleomorphic Adenoma: A Systematic Review. Int J Clin Pediatr Dent. 2020;13(3):284-7. [DOI:10.5005/jp-journals-10005-1776] [PMID] [PMCID]
  8. Hadid F, Hakimi M, Oulghoul O, Benhommad O, Rochdi Y, Raji A. Cystic Adenoid Carcinomas in Ear, Nose and Throat: Unusual Localizations and a Literature Review. Eur J Med Health Sci. 2021;3(2):53-9. [DOI:10.24018/ejmed.2021.3.2.752]
  9. Pusztaszeri M, Rossi ED, Baloch ZW, Faquin WC. Salivary Gland Fine Needle Aspiration and Introduction of the Milan Reporting System. Adv Anat Pathol. 2019;26(2):84-92. [DOI:10.1097/PAP.0000000000000224] [PMID]
  10. Mimica X, McGill M, Hay A, Karassawa Zanoni D, Shah JP, Wong RJ, et al. Distant metastasis of salivary gland cancer: Incidence, management, and outcomes. Cancer. 2020;126(10):2153-62. [DOI:10.1002/cncr.32792] [PMID] [PMCID]
  11. Wright JM, Vered M. Update from the 4th Edition of the World Health Organization Classification of Head and Neck Tumours: Odontogenic and Maxillofacial Bone Tumors. Head Neck Pathol. 2017;11(1):68-77. [DOI:10.1007/s12105-017-0794-1] [PMID] [PMCID]
  12. Speight PM, Barrett AW. Salivary gland tumours: diagnostic challenges and an update on the latest WHO classification. Diagn Histopathol. 2020;26(4):147-58. [DOI:10.1016/j.mpdhp.2020.01.001]
  13. Abel L, Muller-Myhsok B. Maximum-likelihood expression of the transmission/disequilibrium test and power considerations. Am J Hum Genet. 1998;63(2):664-7. [DOI:10.1086/301975] [PMID] [PMCID]
  14. Yu W, Qin X, Jin Y, Li Y, Santiskulvong C, Vu V, et al. Tianshengyuan-1 (TSY-1) regulates cellular Telomerase activity by methylation of TERT promoter. Oncotarget. 2017;8(5):7977-88. [DOI:10.18632/oncotarget.13939] [PMID] [PMCID]
  15. Liu X, Wu G, Shan Y, Hartmann C, von Deimling A, Xing M. Highly prevalent TERT promoter mutations in bladder cancer and glioblastoma. Cell Cycle. 2013;12(10):1637-8. [DOI:10.4161/cc.24662] [PMID] [PMCID]
  16. Salgado C. Epigenetic alterations in the predisposition to and progression of melanoma: Leiden University; 2020.
  17. Arabi Mianroodi A, Jorjandi M. The epidemiology of parotid tumors at the ear, nose and throat department of Shafa educational Hospital, Kerman, Iran. Health Dev J. 2012;1(3):174-81.
  18. Sando Z, Fokouo JV, Mebada AO, Djomou F, A ND, Oyono JL. Epidemiological and histopathological patterns of salivary gland tumors in Cameroon. Pan Afr Med J. 2016;23(1):66. [PMID] [PMCID] [DOI:10.11604/pamj.2016.23.66.5105]
  19. Cunha JL, Coimbra AC, Silva JV, Nascimento IS, Andrade ME, Oliveira CR, et al. Epidemiologic analysis of salivary gland tumors over a 10-years period diagnosed in a northeast Brazilian population. Med Oral Patol Oral Cir Bucal. 2020;25(4):e516-e22. [DOI:10.4317/medoral.23532] [PMID] [PMCID]
  20. Bradley PJ, McGurk M. Incidence of salivary gland neoplasms in a defined UK population. Br J Oral Maxillofac Surg. 2013;51(5):399-403. [DOI:10.1016/j.bjoms.2012.10.002] [PMID]
  21. Taghavi N, Sargolzaei S, Mashhadiabbas F, Akbarzadeh A, Kardouni P. Salivary Gland Tumors: A 15- year Report from Iran. Turk Patol Derg. 2016;32(1):35-9. [DOI:10.5146/tjpath.2015.01336] [PMID]
  22. Campolo Gonzalez A, Ramirez Skinner H, Vargas Diaz A, Leon Ramirez A, Goni Espildora I, Solar Gonzalez A. [Epithelial tumors of salivary glands. Review of 286 pathology reports]. Rev Med Chil. 2018;146(10):1159-66. [DOI:10.4067/S0034-98872018001001159] [PMID]
  23. Noel L, Medford S, Islam S, Muddeen A, Greaves W, Juman S. Epidemiology of salivary gland tumours in an Eastern Caribbean nation: A retrospective study. Ann Med Surg (Lond). 2018;36:148-51. [PMCID] [DOI:10.1016/j.amsu.2018.10.039] [PMID]
  24. Saghravanian N, Ghazi N, Saba M. Clinicopathologic evaluation of salivary gland neoplasms: a 38-year retrospective study in Iran. Ann Diagn Pathol. 2013;17(6):522-5. [PMID] [DOI:10.1016/j.anndiagpath.2013.05.008]
  25. Jones AV, Craig GT, Speight PM, Franklin CD. The range and demographics of salivary gland tumours diagnosed in a UK population. Oral Oncol. 2008;44(4):407-17. [PMID] [DOI:10.1016/j.oraloncology.2007.05.010]
  26. Mejía-Velázquez CP, Durán-Padilla MA, Gómez-Apo E, Quezada-Rivera D, Gaitán-Cepeda LA. Tumors of the salivary gland in Mexicans. A retrospective study of 360 cases. Med Oral Patol Oral Cir Bucal. 2012;17(2):e183. [DOI:10.4317/medoral.17434] [PMID] [PMCID]
  27. Lawal AO, Adisa AO, Kolude B, Adeyemi BF, Olajide MA. A review of 413 salivary gland tumours in the head and neck region. J Clin Exp Dent. 2013;5(5):e218-22. [DOI:10.4317/jced.51143] [PMID] [PMCID]
  28. Otoh EC, Johnson NW, Olasoji H, Danfillo IS, Adeleke OA. Salivary gland neoplasms in Maiduguri, north-eastern Nigeria. Oral Dis. 2005;11(6):386-91. [DOI:10.1111/j.1601-0825.2005.01137.x] [PMID]
  29. Lee Y, Koh J, Kim SI, Won JK, Park CK, Choi SH, et al. The frequency and prognostic effect of TERT promoter mutation in diffuse gliomas. Acta Neuropathol Commun. 2017;5(1):62. [PMCID] [DOI:10.1186/s40478-017-0465-1] [PMID]
  30. Nonoguchi N, Ohta T, Oh JE, Kim YH, Kleihues P, Ohgaki H. TERT promoter mutations in primary and secondary glioblastomas. Acta Neuropathol. 2013;126(6):931-7. [DOI:10.1007/s00401-013-1163-0] [PMID]
  31. Hiraga S, Ohnishi T, Izumoto S, Miyahara E, Kanemura Y, Matsumura H, et al. Telomerase activity and alterations in telomere length in human brain tumors. Cancer Res. 1998;58(10):2117-25.
  32. Liu T, Wang N, Cao J, Sofiadis A, Dinets A, Zedenius J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2014;33(42):4978-84. [DOI:10.1038/onc.2013.446] [PMID]
  33. Alzahrani AS, Alsaadi R, Murugan AK, Sadiq BB. TERT promoter mutations in thyroid cancer. Horm Cancer. 2016;7(3):165-77. [DOI:10.1007/s12672-016-0256-3] [PMID]
  34. Avogbe PH, Manel A, Vian E, Durand G, Forey N, Voegele C, et al. Urinary TERT promoter mutations as non-invasive biomarkers for the comprehensive detection of urothelial cancer. EBioMedicine. 2019;44:431-8. [DOI:10.1016/j.ebiom.2019.05.004] [PMID] [PMCID]
  35. Taylor AS, Newell B, Chinnaiyan AM, Hafez KS, Weizer AZ, Spratt DE, et al. TERT Promoter Mutations in Keratinizing and Nonkeratinizing Squamous Metaplasia of the Urinary Tract. Eur Urol Open Sci. 2022;35:74-8. [PMCID] [DOI:10.1016/j.euros.2021.11.007] [PMID]
  36. Martins F, Martins C, Fernandes MS, Andrade MI, Lopes JM, Soares P, et al. TERT Promoter Mutational Status in the Management of Cutaneous Melanoma: Comparison with Sentinel Lymph Node Biopsy. Dermatology. 2022;238(3):507-16. [DOI:10.1159/000518219] [PMID]
  37. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 2013;339(6122):957-9. [PMCID] [DOI:10.1126/science.1229259] [PMID]
  38. Zhang Y, Chen Y, Yang C, Seger N, Hesla AC, Tsagkozis P, et al. TERT promoter mutation is an objective clinical marker for disease progression in chondrosarcoma. Mod Pathol. 2021;34(11):2020-7. [DOI:10.1038/s41379-021-00848-0] [PMID] [PMCID]
  39. Ventura Ferreira MS, Crysandt M, Braunschweig T, Jost E, Voss B, Bouillon A-S, et al. Presence of TERT promoter mutations is a secondary event and associates with elongated telomere length in myxoid liposarcomas. Int J Mol Sci. 2018;19(2):608. [DOI:10.3390/ijms19020608] [PMID] [PMCID]
  40. Pilsworth JA, Cochrane DR, Xia Z, Aubert G, Farkkila AEM, Horlings HM, et al. TERT promoter mutation in adult granulosa cell tumor of the ovary. Mod Pathol. 2018;31(7):1107-15. [DOI:10.1038/s41379-018-0007-9] [PMID]
  41. Lee H, Jin J-D, La B-M, Park W-J, Choi I-J, Lee J-H. TERT promoter mutation, telomere length, and TERT expression in gastric cancer. 2016.
  42. Duarte MC, Babeto E, Leite KR, Miyazaki K, Borim AA, Rahal P, et al. Expression of TERT in precancerous gastric lesions compared to gastric cancer. Braz J Med Biol Res. 2011;44(2):100-4. [DOI:10.1590/S0100-879X2010007500143] [PMID]
  43. Xu B, Drill E, Ho A, Ho A, Dunn L, Pireto-Granada CN, et al. Predictors of outcome in adenoid cystic carcinoma of salivary glands: a clinicopathologic study with correlation between MYB fusion and protein expression. Am Jl Surg Pathol. 2017;41(10):1422. [DOI:10.1097/PAS.0000000000000918] [PMID] [PMCID]
  44. Dillon PM, Chakraborty S, Moskaluk CA, Joshi PJ, Thomas CY. Adenoid cystic carcinoma: A review of recent advances, molecular targets, and clinical trials. Head Neck. 2016;38(4):620-7. [DOI:10.1002/hed.23925] [PMID] [PMCID]
  45. Patel KP, Vonderheide RH. Telomerase as a tumor-associated antigen for cancer immunotherapy. Cytotechnology. 2004;45(1):91-9. [DOI:10.1007/s10616-004-5132-2] [PMID] [PMCID]
  46. Zhou J, Li T, Geng X, Sui L, Wang F. Antisense oligonucleotide repress telomerase activity via manipulating alternative splicing or translation. Biochem Biophys Res Commun. 2021;582:118-24. [DOI:10.1016/j.bbrc.2021.10.034] [PMID]
  47. Guterres AN, Villanueva J. Targeting telomerase for cancer therapy. Oncogene. 2020;39(36):5811-24. [DOI:10.1038/s41388-020-01405-w] [PMID] [PMCID]
  48. Kim H, Ahn D, Sohn JH, Kim Y-H, Lee J-H, Lee H. TERT promoter mutation and telomere length in salivary gland tumors. Pathol Oncol Res. 2018;24(3):697-8. [DOI:10.1007/s12253-017-0275-6] [PMID]
  49. Cormier C, Agarwal S. Myoepithelial Carcinoma Ex-Pleomorphic Adenoma: A Rare Pathology Misdiagnosed as Pleomorphic Adenoma; With a Novel TERT Promoter Mutation and High PD-L1 Expression. Head Neck Pathol. 2022;16(1):322-30. [DOI:10.1007/s12105-021-01346-0] [PMID] [PMCID]
Iranian Journal of Pathology
Volume 18, Issue 1
Winter 2023
Pages 64-74

  • Receive Date 28 June 2022
  • Revise Date 12 October 2022
  • Accept Date 15 November 2022

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