Молекулярно-генетические маркеры как факторы риска развития рака щитовидной железы
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Rogova M.O., Novosad S.V., Martirosian N.S., et al. Molecular markers as risk factors for thyroid cancer. Therapeutic Archive. 2019; 91 (10): 119–123. DOI: 10.26442/00403660.2019.10.000357
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Ключевые слова: рак щитовидной железы, генетические мутации, атипия неопределенного значения.
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Thyroid cancer is the most common malignant tumor of the endocrine system. An increase in the incidence of thyroid cancer has been noted over the past decade, mainly due to papillary cancer. The influence of environmental factors, increased availability of medical care, including sensitive diagnostic tests, such as ultrasound and fine-needle aspiration (FNA), can affect the fact of the growth of this incidence. Palpation of thyroid gland has very low diagnostic value for detecting thyroid cancer, while thyroid ultrasound and FNA can detect malignant tumors in 20% of cases. Today, the FNA is the fastest, most accurate, economically accessible, and quite safe method for cytological diagnosis of the thyroid nodules. And molecular genetic testing of FNA samples could serve as an additional reliable diagnostic tool in the case of atypia of undetermined significance.
Keywords: thyroid cancer, genetic mutations, atypia of undetermined significance.
2. Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, Penberthy L. Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017 Apr;26(4):632-41. doi: 10.1158/1055-9965.EPI-16-0520
3. Miki H, Oshimo K, Inoue H, et al. Diagnosis and surgical treatment of small papillary carcinomas of the thyroid gland. J Surg Oncol. 1993 Oct;54(2):78-80; discus. 80-1. doi: 10.1002/jso.2930540204
4. Nikiforov YE. Thyroid tumors: Classification and general considerations. In: Nikiforov YE, Biddinger PW, Thompson LDR, eds. Diagnostic pathology and molecular genetcis of the thyroid. Baltimore: Lippincott Williams & Wilkins, 2009. P. 94-102.
5. Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid. 2009;19(12):1351-61. doi: 10.1089/thy.2009.0240
6. Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009 Nov;132(5):658-65. doi: 10.1309/AJCPPHLWMI3JV4LA
7. Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011;96:3390-7. doi: 10.1210/jc.2011-1469
8. Haugen BR, Alexander EK, Bible KC, et al. American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020. Review
9. Nikiforova MN, Mercurio S, Wald AI, Barbi de Moura M, Callenberg K, Santana dos Santos L, Gooding WE, Yip L, Ferris RL, Nikiforov YE. Analytical Performance of the ThyroSeq v3 Genomic Classifier for Cancer Diagnosis in Thyroid Nodules. Cancer. 2018. doi: 10.1002/cncr.31245
10. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC – RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003;63(7):1454-7.
11. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12(2):245-62. doi: 10.1677/erc.1.0978
12. Knauf JA, Ma X, Smith EP, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005;65(10):4238-45. doi: 10.1158/0008-5472.CAN-05-0047
13. Namba H, Nakashima M, Hayashi T, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003;88(9):4393-7. doi: 10.1210/jc.2003-030305
14. Hou P, Liu D, Shan Y, et al. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res. 2007;13(4):1161-70. doi: 10.1158/1078-0432.CCR-06-1125
15. Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/ PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22(29):4578-80. doi: 10.1038/sj.onc.1206706
16. Basolo F, Torregrossa L, Giannini R, et al. Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J Clin Endocrinol Metab. 2010;95(9):4197-205. doi: 10.1210/jc.2010-0337
17. Xing M, Westra WH, Tufano RP, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005;90(12):6373-9. doi: 10.1210/jc.2005-0987
18. Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab. 2008;93(10):3943-9. doi: 10.1210/jc.2008-0607
19. O’Neill CJ, Bullock M, Chou A, et al. BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer. Surgery. 2010;148(6):1139-45, discus. 1145-6. doi: 10.1016/j.surg.2010.09.005
20. Yip L, Nikiforova MN, Carty SE, et al. Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation. Surgery. 2009;146(6):1215-23. doi: 10.1016/j.surg.2009.09.011
21. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol. 2010;321(1):86-93. doi: 10.1016/j.mce.2009.10.012
22. Lee X, Gao M, Ji Y, et al. Analysis of differential BRAF(V600E) mutational status in high aggressive papillary thyroid microcarcinoma. Ann Surg Oncol. 2009;16(2):240-5. doi: 10.1245/s10434-008-0233-3
23. Xing M. BRAF V600E mutation and papillary thyroid cancer. JAMA. 2013 Aug 7;310(5):535. doi: 10.1001/jama.2013.8592
24. Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE. Prevalence of RAS mutations in thyroid neoplasia. Clin Endocrinol (Oxf). 1999;50(4):529-35. doi: 10.1046/j.1365-2265.1999.00704.x
25. Basolo F, Pisaturo F, Pollina LE, et al. N-RAS mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression. Thyroid. 2000;10(1):19-23. doi: 10.1089/thy.2000.10.19
26. Adeniran AJ, Zhu Z, Gandhi M, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006;30(2):216-2. doi: 10.1097/01.pas.0000176432.73455.1b
27. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of RAS mutations. Am J Clin Pathol. 2003;120(1):71-7. doi: 10.1309/nd8d-9laj-trct-g6qd
28. Powell DJ Jr, Russell J, Nibu K, et al. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res. 1998;58(23):5523-8.
29. Tallini G, Santoro M, Helie M, et al. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998;4(2):287-94.
30. Nikiforov YE. RET/PTC Rearrangement in Thyroid Tumors. Endocr Pathol. 2002;13(1):3-16. doi: 10.1385/EP:13:1:03
31. Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab. 1998;83(11):4116-22. doi: 10.1210/jcem.83.11.5271
32. Elisei R, Romei C, Vorontsova T, et al. RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults J Clin Endocrinol Metab. 2001 Jul;86(7):3211-6. doi: 10.1210/jc.86.7.3211
33. Saad A, Falciglia M, Steward DL, Nikiforov YE. Amiodarone induced thyrotoxicosis and thyroid cancer: clinical, immunohistochemical, and molecular genetic studies of a case and review of the literature. Arch Pathol Lab Med. 2004;128(7):807-10. doi: 10.1043/1543-2165(2004)128<807:atatcc>2.0.co;2
34. Mochizuki K, Kondo T, Nakazawa T, et al. RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components. Histopathology. 2010;57(3):444-50. doi: 10.1111/j.1365-2559.2010.03646.x
35. Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science. 2000;289(5483):1357-60. doi: 10.1126/science.289.5483.1357
36. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-26. doi: 10.1210/jc.2002-021907
37. French CA, Alexander EK, Cibas ES, et al. Genetic and biological subgroups of low-stage follicular thyroid cancer. Am J Pathol. 2003;162(4):1053-60. doi: 10.1016/S0002-9440(10)63902-8
38. Ohori NP, Nikiforova MN, Schoedel KE, et al. Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”. Cancer Cytopathol. 2010;118(1):17-23. doi: 10.1002/cncy.20063
39. Liu T, Wang N, Cao J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2014 Oct 16;33(42):4978-84. doi: 10.1038/onc.2013.446
40. Xing M, Liu R, Liu X, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014 Sep 1;32(25):2718-26. doi: 10.1200/JCO.2014.55.5094
41. Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El Naggar AK, Xing M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013;20(4):603-10. doi: 10.1530/ERC-13-0210
42. Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, Murugan AK, Guan H, Yu H, Wang Y, Sun H, Shan Z, Teng W, Xing M. TERT Promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab. 2014;99(6):1130-6. doi: 10.1210/jc.2013-4048
43. Vinagre J, Almeida A, Pópulo H, et al. Frequency of TERT promoter mutations in human cancers. Nat Commun. 2013;4:2185. doi: 10.1038/ncomms3185
44. Melo M, da Rocha AG, Vinagre J, Batista R, et al. TERT Promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014;99:E754-E765. doi: 10.1210/jc.2013-3734
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1. [Beltsevich DG, Vanushko VE, Melnichenko GA, Rumyantsev PO, Fadeyev VV, et al. Russian Association of Endocrinologists Clinic Guidelines for Thyroid Nodules Diagnostic and Treatment. Endokrinnaya Khirurgiya = Endocrine Surgery. 2016;1(10):5-12 (In Russ.)]. doi: 10.14341/serg201615-12
2. Noone AM, Cronin KA, Altekruse SF, Howlader N, Lewis DR, Petkov VI, Penberthy L. Cancer Incidence and Survival Trends by Subtype Using Data from the Surveillance Epidemiology and End Results Program, 1992–2013. Cancer Epidemiol Biomarkers Prev. 2017 Apr;26(4):632-41. doi: 10.1158/1055-9965.EPI-16-0520
3. Miki H, Oshimo K, Inoue H, et al. Diagnosis and surgical treatment of small papillary carcinomas of the thyroid gland. J Surg Oncol. 1993 Oct;54(2):78-80; discus. 80-1. doi: 10.1002/jso.2930540204
4. Nikiforov YE. Thyroid tumors: Classification and general considerations. In: Nikiforov YE, Biddinger PW, Thompson LDR, eds. Diagnostic pathology and molecular genetcis of the thyroid. Baltimore: Lippincott Williams & Wilkins, 2009. P. 94-102.
5. Nikiforova MN, Nikiforov YE. Molecular diagnostics and predictors in thyroid cancer. Thyroid. 2009;19(12):1351-61. doi: 10.1089/thy.2009.0240
6. Cibas ES, Ali SZ; NCI Thyroid FNA State of the Science Conference. The Bethesda System For Reporting Thyroid Cytopathology. Am J Clin Pathol. 2009 Nov;132(5):658-65. doi: 10.1309/AJCPPHLWMI3JV4LA
7. Nikiforov YE, Ohori NP, Hodak SP, et al. Impact of mutational testing on the diagnosis and management of patients with cytologically indeterminate thyroid nodules: a prospective analysis of 1056 FNA samples. J Clin Endocrinol Metab. 2011;96:3390-7. doi: 10.1210/jc.2011-1469
8. Haugen BR, Alexander EK, Bible KC, et al. American Thyroid Association Management Guidelines for Adult Patients with Thyroid Nodules and Differentiated Thyroid Cancer: The American Thyroid Association Guidelines Task Force on Thyroid Nodules and Differentiated Thyroid Cancer. Thyroid. 2016 Jan;26(1):1-133. doi: 10.1089/thy.2015.0020. Review
9. Nikiforova MN, Mercurio S, Wald AI, Barbi de Moura M, Callenberg K, Santana dos Santos L, Gooding WE, Yip L, Ferris RL, Nikiforov YE. Analytical Performance of the ThyroSeq v3 Genomic Classifier for Cancer Diagnosis in Thyroid Nodules. Cancer. 2018. doi: 10.1002/cncr.31245
10. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA. High prevalence of BRAF mutations in thyroid cancer: genetic evidence for constitutive activation of the RET/PTC – RAS-BRAF signaling pathway in papillary thyroid carcinoma. Cancer Res. 2003;63(7):1454-7.
11. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005;12(2):245-62. doi: 10.1677/erc.1.0978
12. Knauf JA, Ma X, Smith EP, et al. Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res. 2005;65(10):4238-45. doi: 10.1158/0008-5472.CAN-05-0047
13. Namba H, Nakashima M, Hayashi T, et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J Clin Endocrinol Metab. 2003;88(9):4393-7. doi: 10.1210/jc.2003-030305
14. Hou P, Liu D, Shan Y, et al. Genetic alterations and their relationship in the phosphatidylinositol 3-kinase/Akt pathway in thyroid cancer. Clin Cancer Res. 2007;13(4):1161-70. doi: 10.1158/1078-0432.CCR-06-1125
15. Soares P, Trovisco V, Rocha AS, et al. BRAF mutations and RET/ PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene. 2003;22(29):4578-80. doi: 10.1038/sj.onc.1206706
16. Basolo F, Torregrossa L, Giannini R, et al. Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases. J Clin Endocrinol Metab. 2010;95(9):4197-205. doi: 10.1210/jc.2010-0337
17. Xing M, Westra WH, Tufano RP, et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005;90(12):6373-9. doi: 10.1210/jc.2005-0987
18. Elisei R, Ugolini C, Viola D, et al. BRAF(V600E) mutation and outcome of patients with papillary thyroid carcinoma: a 15-year median follow-up study. J Clin Endocrinol Metab. 2008;93(10):3943-9. doi: 10.1210/jc.2008-0607
19. O’Neill CJ, Bullock M, Chou A, et al. BRAF(V600E) mutation is associated with an increased risk of nodal recurrence requiring reoperative surgery in patients with papillary thyroid cancer. Surgery. 2010;148(6):1139-45, discus. 1145-6. doi: 10.1016/j.surg.2010.09.005
20. Yip L, Nikiforova MN, Carty SE, et al. Optimizing surgical treatment of papillary thyroid carcinoma associated with BRAF mutation. Surgery. 2009;146(6):1215-23. doi: 10.1016/j.surg.2009.09.011
21. Xing M. Prognostic utility of BRAF mutation in papillary thyroid cancer. Mol Cell Endocrinol. 2010;321(1):86-93. doi: 10.1016/j.mce.2009.10.012
22. Lee X, Gao M, Ji Y, et al. Analysis of differential BRAF(V600E) mutational status in high aggressive papillary thyroid microcarcinoma. Ann Surg Oncol. 2009;16(2):240-5. doi: 10.1245/s10434-008-0233-3
23. Xing M. BRAF V600E mutation and papillary thyroid cancer. JAMA. 2013 Aug 7;310(5):535. doi: 10.1001/jama.2013.8592
24. Esapa CT, Johnson SJ, Kendall-Taylor P, Lennard TW, Harris PE. Prevalence of RAS mutations in thyroid neoplasia. Clin Endocrinol (Oxf). 1999;50(4):529-35. doi: 10.1046/j.1365-2265.1999.00704.x
25. Basolo F, Pisaturo F, Pollina LE, et al. N-RAS mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression. Thyroid. 2000;10(1):19-23. doi: 10.1089/thy.2000.10.19
26. Adeniran AJ, Zhu Z, Gandhi M, et al. Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol. 2006;30(2):216-2. doi: 10.1097/01.pas.0000176432.73455.1b
27. Zhu Z, Gandhi M, Nikiforova MN, Fischer AH, Nikiforov YE. Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of RAS mutations. Am J Clin Pathol. 2003;120(1):71-7. doi: 10.1309/nd8d-9laj-trct-g6qd
28. Powell DJ Jr, Russell J, Nibu K, et al. The RET/PTC3 oncogene: metastatic solid-type papillary carcinomas in murine thyroids. Cancer Res. 1998;58(23):5523-8.
29. Tallini G, Santoro M, Helie M, et al. RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes. Clin Cancer Res. 1998;4(2):287-94.
30. Nikiforov YE. RET/PTC Rearrangement in Thyroid Tumors. Endocr Pathol. 2002;13(1):3-16. doi: 10.1385/EP:13:1:03
31. Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL. Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab. 1998;83(11):4116-22. doi: 10.1210/jcem.83.11.5271
32. Elisei R, Romei C, Vorontsova T, et al. RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults J Clin Endocrinol Metab. 2001 Jul;86(7):3211-6. doi: 10.1210/jc.86.7.3211
33. Saad A, Falciglia M, Steward DL, Nikiforov YE. Amiodarone induced thyrotoxicosis and thyroid cancer: clinical, immunohistochemical, and molecular genetic studies of a case and review of the literature. Arch Pathol Lab Med. 2004;128(7):807-10. doi: 10.1043/1543-2165(2004)128<807:atatcc>2.0.co;2
34. Mochizuki K, Kondo T, Nakazawa T, et al. RET rearrangements and BRAF mutation in undifferentiated thyroid carcinomas having papillary carcinoma components. Histopathology. 2010;57(3):444-50. doi: 10.1111/j.1365-2559.2010.03646.x
35. Kroll TG, Sarraf P, Pecciarini L, et al. PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science. 2000;289(5483):1357-60. doi: 10.1126/science.289.5483.1357
36. Nikiforova MN, Lynch RA, Biddinger PW, et al. RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab. 2003;88(5):2318-26. doi: 10.1210/jc.2002-021907
37. French CA, Alexander EK, Cibas ES, et al. Genetic and biological subgroups of low-stage follicular thyroid cancer. Am J Pathol. 2003;162(4):1053-60. doi: 10.1016/S0002-9440(10)63902-8
38. Ohori NP, Nikiforova MN, Schoedel KE, et al. Contribution of molecular testing to thyroid fine-needle aspiration cytology of “follicular lesion of undetermined significance/atypia of undetermined significance”. Cancer Cytopathol. 2010;118(1):17-23. doi: 10.1002/cncy.20063
39. Liu T, Wang N, Cao J, et al. The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas. Oncogene. 2014 Oct 16;33(42):4978-84. doi: 10.1038/onc.2013.446
40. Xing M, Liu R, Liu X, et al. BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence. J Clin Oncol. 2014 Sep 1;32(25):2718-26. doi: 10.1200/JCO.2014.55.5094
41. Liu X, Bishop J, Shan Y, Pai S, Liu D, Murugan AK, Sun H, El Naggar AK, Xing M. Highly prevalent TERT promoter mutations in aggressive thyroid cancers. Endocr Relat Cancer. 2013;20(4):603-10. doi: 10.1530/ERC-13-0210
42. Liu X, Qu S, Liu R, Sheng C, Shi X, Zhu G, Murugan AK, Guan H, Yu H, Wang Y, Sun H, Shan Z, Teng W, Xing M. TERT Promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer. J Clin Endocrinol Metab. 2014;99(6):1130-6. doi: 10.1210/jc.2013-4048
43. Vinagre J, Almeida A, Pópulo H, et al. Frequency of TERT promoter mutations in human cancers. Nat Commun. 2013;4:2185. doi: 10.1038/ncomms3185
44. Melo M, da Rocha AG, Vinagre J, Batista R, et al. TERT Promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas. J Clin Endocrinol Metab. 2014;99:E754-E765. doi: 10.1210/jc.2013-3734
ФГАОУ ВО «Первый Московский государственный медицинский университет им. И.М. Сеченова» Минздрава России (Сеченовский Университет), Москва, Россия
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M.O. Rogova, S.V. Novosad, N.S. Martirosian, L.V. Trukhina, N.A. Petunina
Sechenov First Moscow State Medical University (Sechenov University), Moscow, Russia