Absence of Hotspot TERT Promoter Mutations in Brazilian Patients with Breast
Keywords:
Breast carcinomas; TERT promoter mutations, early detectionAbstract
Breast cancer is the most common malignancy in women, with increasing rates worldwide. Breast carcinomas are considered a heterogeneous complex disease and despite several studies regarding its molecular aspects, some high-risk genes have not been reported in certain populations. Hotspot mutations (c.-124 bp G>A and c.-146 bp G>A) in the telomerase reverse transcriptase (TERT) promoter in several types of solid tumors has been recently described. However, no extensive studies have evaluated such sequence alterations in breast carcinoma. In this study, we aimed to determine the frequency of hotspot TERT promoter mutations using Sanger sequencing in a series of 99 Brazilian patients with breast cancer. The mutation analysis showed the absence of mutations in the hotspots of the TERT promoter but revealed a high frequency of the rs2853669 minor allele. We can conclude that TERT somatic hotspot mutations are not a contributing factor in breast cancer carcinogenesis in the Brazilian population.
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References
1. Siegel RL, Miller KD, Jemal A. Cancer statistics, 2019. CA: a cancer journal for clinicians. 2019;69(1):7–34.
2. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 10 de agosto de 2014;5(3):412–24.
3. Hanby AM, walker C. Tavassoli FA, Devilee P: Pathology and Genetics: Tumours of the Breast and Female Genital Organs. WHO Classification of Tumours series - volume IV. Lyon, France: IARC Press. Breast Cancer Research. 31 de março de 2004;6(3):133.
4. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol. fevereiro de 2011;5(1):5–23.
5. Bandyopadhyay S, Bluth MH, Ali-Fehmi R. Breast Carcinoma: Updates in Molecular Profiling 2018. Clin Lab Med. 2018;38(2):401–20.
6. Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. Comprehensive molecular portraits of human breast tumours. Nature. outubro de 2012;490(7418):61–70.
7. Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. junho de 2016;534(7605):47–54.
8. Bertucci F, Chaffanet M, Birnbaum D. An ICGC major achievement in breast cancer: a comprehensive catalog of mutations and mutational signatures. Chin Clin Oncol. 2017;6(1):4.
9. Russnes HG, Lingjærde OC, Børresen-Dale A-L, Caldas C. Breast Cancer Molecular Stratification: From Intrinsic Subtypes to Integrative Clusters. Am J Pathol. outubro de 2017;187(10):2152–62.
10. Russnes HG, Vollan HKM, Lingjærde OC, Krasnitz A, Lundin P, Naume B, et al. Genomic architecture characterizes tumor progression paths and fate in breast cancer patients. Sci Transl Med. 30 de junho de 2010;2(38):38ra47.
11. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, et al. TERT promoter mutations in familial and sporadic melanoma. Science. 22 de fevereiro de 2013;339(6122):959–61.
12. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 22 de fevereiro de 2013;339(6122):957–9.
13. Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA. 9 de abril de 2013;110(15):6021–6.
14. Vinagre J, Almeida A, Pópulo H, Batista R, Lyra J, Pinto V, et al. Frequency of TERT promoter mutations in human cancers. Nature Communications. 2013;4:2185.
15. Heidenreich B, Rachakonda PS, Hemminki K, Kumar R. TERT promoter mutations in cancer development. Current Opinion in Genetics & Development. fevereiro de 2014;24:30–7.
16. Campanella NC, Celestino R, Pestana A, Scapulatempo-Neto C, de Oliveira AT, Brito MJ, et al. Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs). Eur J Hum Genet. junho de 2015;23(6):877–9.
17. Campanella NC, Penna V, Abrahão-Machado LF, Cruvinel-Carloni A, Ribeiro G, Soares P, et al. TERT promoter mutations in soft tissue sarcomas. Int J Biol Markers. 28 de fevereiro de 2016;31(1):e62-67.
18. Cárcano FM, Vidal DO, van Helvoort Lengert A, Neto CS, Queiroz L, Marques H, et al. Hotspot TERT promoter mutations are rare events in testicular germ cell tumors. Tumour Biol. abril de 2016;37(4):4901–7.
19. Vazquez V de L, Vicente AL, Carloni A, Berardinelli G, Soares P, Scapulatempo C, et al. Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas. Melanoma Research. abril de 2016;26(2):93–9.
20. Cruvinel-Carloni A, Yamane L, Scapulatempo-Neto C, Guimarães D, Reis RM. Absence of TERT promoter mutations in colorectal precursor lesions and cancer. Genet Mol Biol. março de 2018;41(1):82–4.
21. Yoshida M, Ogawa R, Yoshida H, Maeshima A, Kanai Y, Kinoshita T, et al. TERT promoter mutations are frequent and show association with MED12 mutations in phyllodes tumors of the breast. British Journal of Cancer. 20 de outubro de 2015;113(8):1244–8.
22. Piscuoglio S, Ng CK, Murray M, Burke KA, Edelweiss M, Geyer FC, et al. Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression. J Pathol. março de 2016;238(4):508–18.
23. Shimoi T, Yoshida M, Kitamura Y, Yoshino T, Kawachi A, Shimomura A, et al. TERT promoter hotspot mutations in breast cancer. Breast Cancer. maio de 2018;25(3):292–6.
24. WHO C of T. WHO Classification of Tumours [Internet]. [citado 9 de outubro de 2020]. Disponível em: https://whobluebooks.iarc.fr/
25. Batista R, Cruvinel-Carloni A, Vinagre J, Peixoto J, Catarino TA, Campanella NC, et al. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism. Int J Cancer. 15 de 2016;139(2):414–23.
26. NCBI G. TERT telomerase reverse transcriptase [Homo sapiens (human)] - Gene - NCBI [Internet]. [citado 9 de outubro de 2020]. Disponível em: https://www.ncbi.nlm.nih.gov/gene/7015
27. Jiang Y, Chen C, Chen S-M, Wang Y-Q, Xu Y, Wang Y, et al. Telomerase reverse transcriptase promotes the proliferation of human laryngeal carcinoma cells through activation of the activator protein 1. Oncology Letters. 1o de julho de 2013;6(1):75–80.
28. Park C-K, Lee S-H, Kim JY, Kim JE, Kim TM, Lee S-T, et al. Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma. Oncotarget. 30 de maio de 2014;5(10):3399–407.
29. Spiegl-Kreinecker S, Lötsch D, Ghanim B, Pirker C, Mohr T, Laaber M, et al. Prognostic quality of activating TERT promoter mutations in glioblastoma: interaction with the rs2853669 polymorphism and patient age at diagnosis. Neuro-Oncology. setembro de 2015;17(9):1231–40.
30. Mosrati MA, Malmström A, Lysiak M, Krysztofiak A, Hallbeck M, Milos P, et al. TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma. Oncotarget. 30 de junho de 2015;6(18):16663–73.
31. Li Z-Y, Dong Y-L, Feng Y, Zhang Z, Cao X-Z. Polymorphisms in the telomerase reverse transcriptase promoter are associated with risk of breast cancer: A meta-analysis. J Cancer Res Ther. junho de 2016;12(2):1040–4.
32. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. abril de 2013;45(4):371-384e2.
2. Yersal O, Barutca S. Biological subtypes of breast cancer: Prognostic and therapeutic implications. World J Clin Oncol. 10 de agosto de 2014;5(3):412–24.
3. Hanby AM, walker C. Tavassoli FA, Devilee P: Pathology and Genetics: Tumours of the Breast and Female Genital Organs. WHO Classification of Tumours series - volume IV. Lyon, France: IARC Press. Breast Cancer Research. 31 de março de 2004;6(3):133.
4. Prat A, Perou CM. Deconstructing the molecular portraits of breast cancer. Mol Oncol. fevereiro de 2011;5(1):5–23.
5. Bandyopadhyay S, Bluth MH, Ali-Fehmi R. Breast Carcinoma: Updates in Molecular Profiling 2018. Clin Lab Med. 2018;38(2):401–20.
6. Koboldt DC, Fulton RS, McLellan MD, Schmidt H, Kalicki-Veizer J, McMichael JF, et al. Comprehensive molecular portraits of human breast tumours. Nature. outubro de 2012;490(7418):61–70.
7. Nik-Zainal S, Davies H, Staaf J, Ramakrishna M, Glodzik D, Zou X, et al. Landscape of somatic mutations in 560 breast cancer whole-genome sequences. Nature. junho de 2016;534(7605):47–54.
8. Bertucci F, Chaffanet M, Birnbaum D. An ICGC major achievement in breast cancer: a comprehensive catalog of mutations and mutational signatures. Chin Clin Oncol. 2017;6(1):4.
9. Russnes HG, Lingjærde OC, Børresen-Dale A-L, Caldas C. Breast Cancer Molecular Stratification: From Intrinsic Subtypes to Integrative Clusters. Am J Pathol. outubro de 2017;187(10):2152–62.
10. Russnes HG, Vollan HKM, Lingjærde OC, Krasnitz A, Lundin P, Naume B, et al. Genomic architecture characterizes tumor progression paths and fate in breast cancer patients. Sci Transl Med. 30 de junho de 2010;2(38):38ra47.
11. Horn S, Figl A, Rachakonda PS, Fischer C, Sucker A, Gast A, et al. TERT promoter mutations in familial and sporadic melanoma. Science. 22 de fevereiro de 2013;339(6122):959–61.
12. Huang FW, Hodis E, Xu MJ, Kryukov GV, Chin L, Garraway LA. Highly recurrent TERT promoter mutations in human melanoma. Science. 22 de fevereiro de 2013;339(6122):957–9.
13. Killela PJ, Reitman ZJ, Jiao Y, Bettegowda C, Agrawal N, Diaz LA, et al. TERT promoter mutations occur frequently in gliomas and a subset of tumors derived from cells with low rates of self-renewal. Proc Natl Acad Sci USA. 9 de abril de 2013;110(15):6021–6.
14. Vinagre J, Almeida A, Pópulo H, Batista R, Lyra J, Pinto V, et al. Frequency of TERT promoter mutations in human cancers. Nature Communications. 2013;4:2185.
15. Heidenreich B, Rachakonda PS, Hemminki K, Kumar R. TERT promoter mutations in cancer development. Current Opinion in Genetics & Development. fevereiro de 2014;24:30–7.
16. Campanella NC, Celestino R, Pestana A, Scapulatempo-Neto C, de Oliveira AT, Brito MJ, et al. Low frequency of TERT promoter mutations in gastrointestinal stromal tumors (GISTs). Eur J Hum Genet. junho de 2015;23(6):877–9.
17. Campanella NC, Penna V, Abrahão-Machado LF, Cruvinel-Carloni A, Ribeiro G, Soares P, et al. TERT promoter mutations in soft tissue sarcomas. Int J Biol Markers. 28 de fevereiro de 2016;31(1):e62-67.
18. Cárcano FM, Vidal DO, van Helvoort Lengert A, Neto CS, Queiroz L, Marques H, et al. Hotspot TERT promoter mutations are rare events in testicular germ cell tumors. Tumour Biol. abril de 2016;37(4):4901–7.
19. Vazquez V de L, Vicente AL, Carloni A, Berardinelli G, Soares P, Scapulatempo C, et al. Molecular profiling, including TERT promoter mutations, of acral lentiginous melanomas. Melanoma Research. abril de 2016;26(2):93–9.
20. Cruvinel-Carloni A, Yamane L, Scapulatempo-Neto C, Guimarães D, Reis RM. Absence of TERT promoter mutations in colorectal precursor lesions and cancer. Genet Mol Biol. março de 2018;41(1):82–4.
21. Yoshida M, Ogawa R, Yoshida H, Maeshima A, Kanai Y, Kinoshita T, et al. TERT promoter mutations are frequent and show association with MED12 mutations in phyllodes tumors of the breast. British Journal of Cancer. 20 de outubro de 2015;113(8):1244–8.
22. Piscuoglio S, Ng CK, Murray M, Burke KA, Edelweiss M, Geyer FC, et al. Massively parallel sequencing of phyllodes tumours of the breast reveals actionable mutations, and TERT promoter hotspot mutations and TERT gene amplification as likely drivers of progression. J Pathol. março de 2016;238(4):508–18.
23. Shimoi T, Yoshida M, Kitamura Y, Yoshino T, Kawachi A, Shimomura A, et al. TERT promoter hotspot mutations in breast cancer. Breast Cancer. maio de 2018;25(3):292–6.
24. WHO C of T. WHO Classification of Tumours [Internet]. [citado 9 de outubro de 2020]. Disponível em: https://whobluebooks.iarc.fr/
25. Batista R, Cruvinel-Carloni A, Vinagre J, Peixoto J, Catarino TA, Campanella NC, et al. The prognostic impact of TERT promoter mutations in glioblastomas is modified by the rs2853669 single nucleotide polymorphism. Int J Cancer. 15 de 2016;139(2):414–23.
26. NCBI G. TERT telomerase reverse transcriptase [Homo sapiens (human)] - Gene - NCBI [Internet]. [citado 9 de outubro de 2020]. Disponível em: https://www.ncbi.nlm.nih.gov/gene/7015
27. Jiang Y, Chen C, Chen S-M, Wang Y-Q, Xu Y, Wang Y, et al. Telomerase reverse transcriptase promotes the proliferation of human laryngeal carcinoma cells through activation of the activator protein 1. Oncology Letters. 1o de julho de 2013;6(1):75–80.
28. Park C-K, Lee S-H, Kim JY, Kim JE, Kim TM, Lee S-T, et al. Expression level of hTERT is regulated by somatic mutation and common single nucleotide polymorphism at promoter region in glioblastoma. Oncotarget. 30 de maio de 2014;5(10):3399–407.
29. Spiegl-Kreinecker S, Lötsch D, Ghanim B, Pirker C, Mohr T, Laaber M, et al. Prognostic quality of activating TERT promoter mutations in glioblastoma: interaction with the rs2853669 polymorphism and patient age at diagnosis. Neuro-Oncology. setembro de 2015;17(9):1231–40.
30. Mosrati MA, Malmström A, Lysiak M, Krysztofiak A, Hallbeck M, Milos P, et al. TERT promoter mutations and polymorphisms as prognostic factors in primary glioblastoma. Oncotarget. 30 de junho de 2015;6(18):16663–73.
31. Li Z-Y, Dong Y-L, Feng Y, Zhang Z, Cao X-Z. Polymorphisms in the telomerase reverse transcriptase promoter are associated with risk of breast cancer: A meta-analysis. J Cancer Res Ther. junho de 2016;12(2):1040–4.
32. Bojesen SE, Pooley KA, Johnatty SE, Beesley J, Michailidou K, Tyrer JP, et al. Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat Genet. abril de 2013;45(4):371-384e2.
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Published
2020-12-30
How to Cite
Causin, R. L., Abrão, S. de F., Cruvinel-Carloni, A., Evangelista, A. F., Souza, C. de P., Neuber, A. C., … Marques, M. M. C. (2020). Absence of Hotspot TERT Promoter Mutations in Brazilian Patients with Breast. Manuscripta Medica, 3, 14–20. Retrieved from https://manuscriptamedica.com.br/revista/index.php/mm/article/view/39
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