The Clinical Significance of BRAF<sup>V600E</sup> Mutation in Papillary Thyroid Cancer_CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

Authors：

 CHENQiang ^1,2 ,  ZHUJing-qiang ¹

1. Department of Thyroid and Breast Surgery, West China Hospital, Sichuan University, Chengdu 610041, Sichuan Province, China;
2. West China School of Medicine, Sichuan University, Chengdu 610041, Sichuan Province, China;

Corresponding author：

ZHUJing-qiang, Email: zjq-wkys@163.com

Keywords：

BRAF^V600E mutation; Papillary thyroid cancer; Fine needle aspiration cytology

DOI：

10.7507/1007-9424.20140266

Video：

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Objective To summarize the significance of BRAF^V600E mutation for the diagnosis, treatment, and prognosis of papillary thyroid cancer (PTC). Methods Related literatures which were published in recent years for exploring the relationship of BRAF^V600E mutation and PTC were collected and reviewed. Results The BRAF^V600E mutation was the most common mutant type in PTC, which played an important role in the oncogenesis and development of PTC. In addition, this type of mutation was closely associated with aggressive behavior and poor prognosis of PTC. The BRAF^V600E testing in fine needle aspiration (FNA) samples of thyroid nodule not only facilitated to improve the diagnostic accuracy of PTC, but also helped ensure the recurrence risk classification, selection of surgical treatment, and follow-up planning. Conclusion BRAF^V600E mutation was prevalent in PTC and had important significance both in diagnosis and prognostic evaluation of PTC.

Citation： CHENQiang, ZHUJing-qiang. The Clinical Significance of BRAF^V600E Mutation in Papillary Thyroid Cancer. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2014, 21(9): 1108-1113. doi: 10.7507/1007-9424.20140266 Copy

1.	Shin JJ, Milas M. Detection of disease recurrence in differentiated thyroid cancer[J]. Minerva Chir, 2010, 65(1):101-116.
2.	Dillon LW, Lehman CE, Wang YH. The role of fragile sites in sporadic papillary thyroid carcinoma[J]. J Thyroid Res, 2012, 2012:927683.
3.	Venkat R, Guerrero MA. Recent advances in the surgical treatment of differentiated thyroid vancer:a comprehensive review[J]. Sci World J, 2013, 2013:425136.
4.	孙嘉伟, 许晓君, 蔡秋茂, 等. 中国甲状腺癌发病趋势分析[J]. 中国肿瘤, 2013, 22(9):690-693.
5.	Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002[J]. JAMA, 2006, 295(18):2164-2167.
6.	Dal Maso L, Bosetti C, La Vecchia C, et al. Risk factors for thyroid cancer:an epidemiological review focused on nutritional factors[J]. Cancer Causes Control, 2009, 20(1):75-86.
7.	Sinnott B, Ron E, Schneider AB. Exposing the thyroid to radiation:a review of its current extent, risks, and implications[J]. Endocr Rev, 2010, 31(5):756-773.
8.	Haymart MR, Repplinger DJ, Leverson GE, et al. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage[J]. J Clin Endocrinol Metab, 2008, 93(3):809-814.
9.	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]. J Clin Endocrinol Metab, 2008, 93(10):3943-3949.
10.	Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid:a meta-analysis[J]. Cancer, 2007, 110(1):38-46.
11.	Xing M. BRAF mutation in papillary thyroid cancer:pathogenic role, molecular bases, and clinical implications[J]. Endocr Rev, 2007, 28(7):742-762.
12.	Kwak JY, Kim EK, Chung WY, et al. Association of BRAFV600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma[J]. Radiology, 2009, 253(3):854-860.
13.	Zagzag J, Pollack A, Dultz L, et al. Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma[J]. Surgery, 2013, 154(6):1199-1204.
14.	Caronia LM, Phay JE, Shah MH. Role of BRAF in thyroid oncogenesis[J]. Clin Cancer Res, 2011, 17(24):7511-7517.
15.	Zafon C, Obiols G. The mitogen-activated protein kinase (MAPK) signaling pathway in papillary thyroid cancer. From the molecular bases to clinical practice[J]. Endocrinol Nutr, 2009, 56(4):176-186.
16.	Tang KT, Lee CH. BRAF mutation in papillary thyroid carcinoma:pathogenic role and clinical implications[J]. J Chin Med Assoc, 2010, 73(3):113-128.
17.	Xing M. BRAF mutation in thyroid cancer[J]. Endocr Relat Cancer, 2005, 12(2):245-262.
18.	Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer[J]. Nature, 2002, 417(6892):949-954.
19.	Deng G, Bell I, Crawley S, et al. BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer[J]. Clin Cancer Res, 2004, 10(1 Pt 1):191-195.
20.	Singer G, Oldt R 3^rd, Cohen Y, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma[J]. J Natl Cancer Inst, 2003, 95(6):484-486.
21.	Brose MS, Volpe P, Feldman M, et al. BRAF and RAS mutations in human lung cancer and melanoma[J]. Cancer Res, 2002, 62(23):6997-7000.
22.	Cohen Y, Xing M, Mambo E, et al. BRAF mutation in papillary thyroid carcinoma[J]. J Natl Cancer Inst, 2003, 95(8):625-627.
23.	Garnett MJ, Marais R. Guilty as charged:B-RAF is a human oncogene[J]. Cancer Cell, 2004, 6(4):313-319.
24.	Jung CK, Im SY, Kang YJ, et al. Mutational patterns and novel mutations of the BRAF gene in a large cohort of Korean patients with papillary thyroid carcinoma[J]. Thyroid, 2012, 22(8):791-797.
25.	Lee KC, Li C, Schneider EB, et al. Is BRAF mutation associated with lymph node metastasis in patients with papillary thyroid cancer?[J]. Surgery, 2012, 152(6):977-983.
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[J]. Am J Surg Pathol, 2006, 30(2):216-222.
27.	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[J]. Cancer Res, 2005, 65(10):4238-4245.
28.	Espinosa AV, Porchia L, Ringel MD. Targeting BRAF in thyroid cancer[J]. Br J Cancer, 2007, 96(1):16-20.
29.	Ciampi R, Nikiforov YE. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis[J]. Endocrinology, 2007, 148(3):936-941.
30.	Mesa C Jr, Mirza M, Mitsutake N, et al. Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling[J]. Cancer Res, 2006, 66(13):6521-6529.
31.	Romei C, Ciampi R, Faviana P, et al. BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer[J]. Endocr Relat Cancer, 2008, 15(2):511-520.
32.	Romei C, Elisei R. RET/PTC translocations and clinico-pathological features in human papillary thyroid carcinoma[J]. Front Endocrinol (Lausanne), 2012, 3:54.
33.	Cyniak-Magierska A, Brzeziańska E, Januszkiewicz-Caulier J, et al. Prevalence of RAS point mutations in papillary thyroid carcinoma; a novel mutation at codon 31 of K-RAS[J]. Exp Clin Endocrinol Diabetes, 2007, 115(9):594-599.
34.	Sapio MR, Posca D, Troncone G, et al. Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA)[J]. Eur J Endocrinol, 2006, 154(2):341-348.
35.	Kim SK, Kim DL, Han HS, et al. Pyrosequencing analysis for detection of a BRAFV600E mutation in an FNAB specimen of thyroid nodules[J]. Diagn Mol Pathol, 2008, 17(2):118-125.
36.	Adeniran AJ, Theoharis C, Hui P, et al. Reflex BRAF testing in thyroid fine-needle aspiration biopsy with equivocal and positive interpretation:a prospective study[J]. Thyroid, 2011, 21(7):717-723.
37.	Liu S, Gao A, Zhang B, et al. Assessment of molecular testing in fine-needle aspiration biopsy samples:an experience in a Chinese population[J]. Exp Mol Pathol, 2014, 97(2):292-297.
38.	关海霞, 邢明照. BRAFT1799A基因突变在甲状腺乳头状癌临床诊治中的意义[J]. 中华内分泌代谢杂志, 2011, 27(6):525-528.
39.	Miller CJ, Cheung M, Sharma A, et al. Method of mutation analysis may contribute to discrepancies in reports of (V599E) BRAF mutation frequencies in melanocytic neoplasms[J]. J Invest Dermatol, 2004, 123(5):990-992.
40.	Li Y, Nakamura M, Kakudo K. Targeting of the BRAF gene in papillary thyroid carcinoma (review)[J]. Oncol Rep, 2009, 22(4):671-681.
41.	Pacini F, Castagna MG, Brilli L, et al. Differentiated thyroid cancer:ESMO clinical recommendations for diagnosis, treatment and follow-up[J]. Ann Oncol, 2009, 20 Suppl 4:143-146.
42.	American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer[J]. Thyroid, 2009, 19(11):1167-1214.
43.	Hundahl SA, Fleming ID, Fremgen AM, et al. A national cancer data base report on 53856 cases of thyroid carcinoma treated in the U.S., 1985-1995[J]. Cancer, 1998, 83(12):2638-2648.
44.	Dutenhefner SE, Marui S, Santos AB, et al. BRAF:a tool in the decision to perform elective neck dissection?[J]. Thyroid, 2013, 23(12):1541-1546.
45.	Oler G, Cerutti JM. High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas:correlation with more aggressive phenotype and decreased expression of iodide-metabolizing genes[J]. Cancer, 2009, 115(5):972-980.
46.	Riesco-Eizaguirre G, Gutiérrez-Martínez P, García-Cabezas MA, et al. The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na⁺/I^- targeting to the membrane[J]. Endocr Relat Cancer, 2006, 13(1):257-269.
47.	Mian C, Barollo S, Pennelli G, et al. Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake[J]. Clin Endocrinol (Oxf), 2008, 68(1):108-116.
48.	Durante C, Puxeddu E, Ferretti E, et al. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism[J]. J Clin Endocrinol Metab, 2007, 92(7):2840-2843.
49.	Espadinha C, Santos JR, Sobrinho LG, et al. Expression of iodine metabolism genes in human thyroid tissues:evidence for age and BRAFV600E mutation dependency[J]. Clin Endocrinol (Oxf), 2009, 70(4):629-635.
50.	Ouyang B, Knauf JA, Smith EP, et al. Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo[J]. Clin Cancer Res, 2006, 12(6):1785-1793.
51.	Salvatore G, De Falco V, Salerno P, et al. BRAF is a therapeutic target in aggressive thyroid carcinoma[J]. Clin Cancer Res, 2006, 12(5):1623-1629.
52.	Chiloeches A, Marais R. Is BRAF the Achilles' heel of thyroid cancer?[J]. Clin Cancer Res, 2006, 12(6):1661-1664.
53.	Sala E, Mologni L, Truffa S, et al. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells[J]. Mol Cancer Res, 2008, 6(5):751-759.
54.	Tsai J, Lee JT, Wang W, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity[J]. Proc Natl Acad Sci U S A, 2008, 105(8):3041-3046.
55.	Strumberg D. Sorafenib for the treatment of renal cancer[J]. Expert Opin Pharmacother, 2012, 13(3):407-419.
56.	Kane RC, Farrell AT, Madabushi R, et al. Sorafenib for the treatment of unresectable hepatocellular carcinoma[J]. Oncologist, 2009, 14(1):95-100.
57.	Adnane L, Trail PA, Taylor I, et al. Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature[J]. Methods Enzymol, 2006, 407:597-612.
58.	Ravikumar K, Sridhar B, Bhujanga Rao AK, et al. Sorafenib and its tosylate salt:a multikinase inhibitor for treating cancer[J]. Acta Crystallogr C, 2011, 67(Pt 1):o29-o32.
59.	Schlumberger M, Brose M, Elisei R, et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer[J]. Lancet Diabetes Endocrinol, 2014, 2(5):356-358.
60.	Liu D, Liu Z, Condouris S, et al. BRAF V600E maintains proliferation, transformation, and tumorigenicity of BRAF-mutant papillary thyroid cancer cells[J]. J Clin Endocrinol Metab, 2007, 92(6):2264-2271.
61.	Liu D, Hu S, Hou P, et al. Suppression of BRAF/MEK/MAP kinase pathway restores expression of iodide-metabolizing genes in thyroid cells expressing the V600E BRAF mutant[J]. Clin Cancer Res, 2007, 13(4):1341-1349.

1. Shin JJ, Milas M. Detection of disease recurrence in differentiated thyroid cancer[J]. Minerva Chir, 2010, 65(1):101-116.
2. Dillon LW, Lehman CE, Wang YH. The role of fragile sites in sporadic papillary thyroid carcinoma[J]. J Thyroid Res, 2012, 2012:927683.
3. Venkat R, Guerrero MA. Recent advances in the surgical treatment of differentiated thyroid vancer:a comprehensive review[J]. Sci World J, 2013, 2013:425136.
4. 孙嘉伟, 许晓君, 蔡秋茂, 等. 中国甲状腺癌发病趋势分析[J]. 中国肿瘤, 2013, 22(9):690-693.
5. Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973-2002[J]. JAMA, 2006, 295(18):2164-2167.
6. Dal Maso L, Bosetti C, La Vecchia C, et al. Risk factors for thyroid cancer:an epidemiological review focused on nutritional factors[J]. Cancer Causes Control, 2009, 20(1):75-86.
7. Sinnott B, Ron E, Schneider AB. Exposing the thyroid to radiation:a review of its current extent, risks, and implications[J]. Endocr Rev, 2010, 31(5):756-773.
8. Haymart MR, Repplinger DJ, Leverson GE, et al. Higher serum thyroid stimulating hormone level in thyroid nodule patients is associated with greater risks of differentiated thyroid cancer and advanced tumor stage[J]. J Clin Endocrinol Metab, 2008, 93(3):809-814.
9. 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]. J Clin Endocrinol Metab, 2008, 93(10):3943-3949.
10. Lee JH, Lee ES, Kim YS. Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid:a meta-analysis[J]. Cancer, 2007, 110(1):38-46.
11. Xing M. BRAF mutation in papillary thyroid cancer:pathogenic role, molecular bases, and clinical implications[J]. Endocr Rev, 2007, 28(7):742-762.
12. Kwak JY, Kim EK, Chung WY, et al. Association of BRAFV600E mutation with poor clinical prognostic factors and US features in Korean patients with papillary thyroid microcarcinoma[J]. Radiology, 2009, 253(3):854-860.
13. Zagzag J, Pollack A, Dultz L, et al. Clinical utility of immunohistochemistry for the detection of the BRAF v600e mutation in papillary thyroid carcinoma[J]. Surgery, 2013, 154(6):1199-1204.
14. Caronia LM, Phay JE, Shah MH. Role of BRAF in thyroid oncogenesis[J]. Clin Cancer Res, 2011, 17(24):7511-7517.
15. Zafon C, Obiols G. The mitogen-activated protein kinase (MAPK) signaling pathway in papillary thyroid cancer. From the molecular bases to clinical practice[J]. Endocrinol Nutr, 2009, 56(4):176-186.
16. Tang KT, Lee CH. BRAF mutation in papillary thyroid carcinoma:pathogenic role and clinical implications[J]. J Chin Med Assoc, 2010, 73(3):113-128.
17. Xing M. BRAF mutation in thyroid cancer[J]. Endocr Relat Cancer, 2005, 12(2):245-262.
18. Davies H, Bignell GR, Cox C, et al. Mutations of the BRAF gene in human cancer[J]. Nature, 2002, 417(6892):949-954.
19. Deng G, Bell I, Crawley S, et al. BRAF mutation is frequently present in sporadic colorectal cancer with methylated hMLH1, but not in hereditary nonpolyposis colorectal cancer[J]. Clin Cancer Res, 2004, 10(1 Pt 1):191-195.
20. Singer G, Oldt R 3^rd, Cohen Y, et al. Mutations in BRAF and KRAS characterize the development of low-grade ovarian serous carcinoma[J]. J Natl Cancer Inst, 2003, 95(6):484-486.
21. Brose MS, Volpe P, Feldman M, et al. BRAF and RAS mutations in human lung cancer and melanoma[J]. Cancer Res, 2002, 62(23):6997-7000.
22. Cohen Y, Xing M, Mambo E, et al. BRAF mutation in papillary thyroid carcinoma[J]. J Natl Cancer Inst, 2003, 95(8):625-627.
23. Garnett MJ, Marais R. Guilty as charged:B-RAF is a human oncogene[J]. Cancer Cell, 2004, 6(4):313-319.
24. Jung CK, Im SY, Kang YJ, et al. Mutational patterns and novel mutations of the BRAF gene in a large cohort of Korean patients with papillary thyroid carcinoma[J]. Thyroid, 2012, 22(8):791-797.
25. Lee KC, Li C, Schneider EB, et al. Is BRAF mutation associated with lymph node metastasis in patients with papillary thyroid cancer?[J]. Surgery, 2012, 152(6):977-983.
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[J]. Am J Surg Pathol, 2006, 30(2):216-222.
27. 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[J]. Cancer Res, 2005, 65(10):4238-4245.
28. Espinosa AV, Porchia L, Ringel MD. Targeting BRAF in thyroid cancer[J]. Br J Cancer, 2007, 96(1):16-20.
29. Ciampi R, Nikiforov YE. RET/PTC rearrangements and BRAF mutations in thyroid tumorigenesis[J]. Endocrinology, 2007, 148(3):936-941.
30. Mesa C Jr, Mirza M, Mitsutake N, et al. Conditional activation of RET/PTC3 and BRAFV600E in thyroid cells is associated with gene expression profiles that predict a preferential role of BRAF in extracellular matrix remodeling[J]. Cancer Res, 2006, 66(13):6521-6529.
31. Romei C, Ciampi R, Faviana P, et al. BRAFV600E mutation, but not RET/PTC rearrangements, is correlated with a lower expression of both thyroperoxidase and sodium iodide symporter genes in papillary thyroid cancer[J]. Endocr Relat Cancer, 2008, 15(2):511-520.
32. Romei C, Elisei R. RET/PTC translocations and clinico-pathological features in human papillary thyroid carcinoma[J]. Front Endocrinol (Lausanne), 2012, 3:54.
33. Cyniak-Magierska A, Brzeziańska E, Januszkiewicz-Caulier J, et al. Prevalence of RAS point mutations in papillary thyroid carcinoma; a novel mutation at codon 31 of K-RAS[J]. Exp Clin Endocrinol Diabetes, 2007, 115(9):594-599.
34. Sapio MR, Posca D, Troncone G, et al. Detection of BRAF mutation in thyroid papillary carcinomas by mutant allele-specific PCR amplification (MASA)[J]. Eur J Endocrinol, 2006, 154(2):341-348.
35. Kim SK, Kim DL, Han HS, et al. Pyrosequencing analysis for detection of a BRAFV600E mutation in an FNAB specimen of thyroid nodules[J]. Diagn Mol Pathol, 2008, 17(2):118-125.
36. Adeniran AJ, Theoharis C, Hui P, et al. Reflex BRAF testing in thyroid fine-needle aspiration biopsy with equivocal and positive interpretation:a prospective study[J]. Thyroid, 2011, 21(7):717-723.
37. Liu S, Gao A, Zhang B, et al. Assessment of molecular testing in fine-needle aspiration biopsy samples:an experience in a Chinese population[J]. Exp Mol Pathol, 2014, 97(2):292-297.
38. 关海霞, 邢明照. BRAFT1799A基因突变在甲状腺乳头状癌临床诊治中的意义[J]. 中华内分泌代谢杂志, 2011, 27(6):525-528.
39. Miller CJ, Cheung M, Sharma A, et al. Method of mutation analysis may contribute to discrepancies in reports of (V599E) BRAF mutation frequencies in melanocytic neoplasms[J]. J Invest Dermatol, 2004, 123(5):990-992.
40. Li Y, Nakamura M, Kakudo K. Targeting of the BRAF gene in papillary thyroid carcinoma (review)[J]. Oncol Rep, 2009, 22(4):671-681.
41. Pacini F, Castagna MG, Brilli L, et al. Differentiated thyroid cancer:ESMO clinical recommendations for diagnosis, treatment and follow-up[J]. Ann Oncol, 2009, 20 Suppl 4:143-146.
42. American Thyroid Association (ATA) Guidelines Taskforce on Thyroid Nodules and Differentiated Thyroid Cancer, Cooper DS, Doherty GM, et al. Revised American thyroid association management guidelines for patients with thyroid nodules and differentiated thyroid cancer[J]. Thyroid, 2009, 19(11):1167-1214.
43. Hundahl SA, Fleming ID, Fremgen AM, et al. A national cancer data base report on 53856 cases of thyroid carcinoma treated in the U.S., 1985-1995[J]. Cancer, 1998, 83(12):2638-2648.
44. Dutenhefner SE, Marui S, Santos AB, et al. BRAF:a tool in the decision to perform elective neck dissection?[J]. Thyroid, 2013, 23(12):1541-1546.
45. Oler G, Cerutti JM. High prevalence of BRAF mutation in a Brazilian cohort of patients with sporadic papillary thyroid carcinomas:correlation with more aggressive phenotype and decreased expression of iodide-metabolizing genes[J]. Cancer, 2009, 115(5):972-980.
46. Riesco-Eizaguirre G, Gutiérrez-Martínez P, García-Cabezas MA, et al. The oncogene BRAF V600E is associated with a high risk of recurrence and less differentiated papillary thyroid carcinoma due to the impairment of Na⁺/I^- targeting to the membrane[J]. Endocr Relat Cancer, 2006, 13(1):257-269.
47. Mian C, Barollo S, Pennelli G, et al. Molecular characteristics in papillary thyroid cancers (PTCs) with no 131I uptake[J]. Clin Endocrinol (Oxf), 2008, 68(1):108-116.
48. Durante C, Puxeddu E, Ferretti E, et al. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism[J]. J Clin Endocrinol Metab, 2007, 92(7):2840-2843.
49. Espadinha C, Santos JR, Sobrinho LG, et al. Expression of iodine metabolism genes in human thyroid tissues:evidence for age and BRAFV600E mutation dependency[J]. Clin Endocrinol (Oxf), 2009, 70(4):629-635.
50. Ouyang B, Knauf JA, Smith EP, et al. Inhibitors of Raf kinase activity block growth of thyroid cancer cells with RET/PTC or BRAF mutations in vitro and in vivo[J]. Clin Cancer Res, 2006, 12(6):1785-1793.
51. Salvatore G, De Falco V, Salerno P, et al. BRAF is a therapeutic target in aggressive thyroid carcinoma[J]. Clin Cancer Res, 2006, 12(5):1623-1629.
52. Chiloeches A, Marais R. Is BRAF the Achilles' heel of thyroid cancer?[J]. Clin Cancer Res, 2006, 12(6):1661-1664.
53. Sala E, Mologni L, Truffa S, et al. BRAF silencing by short hairpin RNA or chemical blockade by PLX4032 leads to different responses in melanoma and thyroid carcinoma cells[J]. Mol Cancer Res, 2008, 6(5):751-759.
54. Tsai J, Lee JT, Wang W, et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity[J]. Proc Natl Acad Sci U S A, 2008, 105(8):3041-3046.
55. Strumberg D. Sorafenib for the treatment of renal cancer[J]. Expert Opin Pharmacother, 2012, 13(3):407-419.
56. Kane RC, Farrell AT, Madabushi R, et al. Sorafenib for the treatment of unresectable hepatocellular carcinoma[J]. Oncologist, 2009, 14(1):95-100.
57. Adnane L, Trail PA, Taylor I, et al. Sorafenib (BAY 43-9006, Nexavar), a dual-action inhibitor that targets RAF/MEK/ERK pathway in tumor cells and tyrosine kinases VEGFR/PDGFR in tumor vasculature[J]. Methods Enzymol, 2006, 407:597-612.
58. Ravikumar K, Sridhar B, Bhujanga Rao AK, et al. Sorafenib and its tosylate salt:a multikinase inhibitor for treating cancer[J]. Acta Crystallogr C, 2011, 67(Pt 1):o29-o32.
59. Schlumberger M, Brose M, Elisei R, et al. Definition and management of radioactive iodine-refractory differentiated thyroid cancer[J]. Lancet Diabetes Endocrinol, 2014, 2(5):356-358.
60. Liu D, Liu Z, Condouris S, et al. BRAF V600E maintains proliferation, transformation, and tumorigenicity of BRAF-mutant papillary thyroid cancer cells[J]. J Clin Endocrinol Metab, 2007, 92(6):2264-2271.
61. Liu D, Hu S, Hou P, et al. Suppression of BRAF/MEK/MAP kinase pathway restores expression of iodide-metabolizing genes in thyroid cells expressing the V600E BRAF mutant[J]. Clin Cancer Res, 2007, 13(4):1341-1349.

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The Clinical Significance of BRAF^V600E Mutation in Papillary Thyroid Cancer

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CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY

The Clinical Significance of BRAFV600E Mutation in Papillary Thyroid Cancer

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The Clinical Significance of BRAF^V600E Mutation in Papillary Thyroid Cancer