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The Biology of Thyroid Oncogenesis

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Part of the book series: Cancer Treatment and Research ((CTAR,volume 153))

Abstract

Over the past 20 years, our understanding of the molecular biology of thyroid cancer has advanced significantly. These new insights have in turn unleashed a vast potential for clinical application across the diagnostic, prognostic, and therapeutic spectrum. A classic example of this is the identification of the RET proto–oncogene responsible for hereditary medullary thyroid cancer (MTC), which has led to earlier diagnosis by genetic screening, and thus better patient outcomes. It is one of the few hereditary cancers for which at–risk individuals can be identified by genetic testing and be advised a prophylactic thyroidectomy, as they will certainly develop MTC over their lifetime.

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References

  1. Kondo T, Ezzat S, Asa SL (2006) Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer 6:292–306

    Article  CAS  PubMed  Google Scholar 

  2. Lemoine NR, Mayall ES, Wyllie FS et al (1989) High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis. Oncogene 4:159–164

    CAS  PubMed  Google Scholar 

  3. Nikiforova MN, Lynch RA, Biddinger PW et al (2003) RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J Clin Endocrinol Metab 88:2318–2326

    Article  CAS  PubMed  Google Scholar 

  4. Shinohara M, Chung YJ, Saji M, Ringel MD (2007) AKT in thyroid tumorigenesis and progression. Endocrinology 148:942–947

    Article  CAS  PubMed  Google Scholar 

  5. Ito T, Seyama T, Mizuno T et al (1992) Unique association of p53 mutations with undifferentiated but not with differentiated carcinomas of the thyroid gland. Cancer Res 52:1369–1371

    CAS  PubMed  Google Scholar 

  6. Joneson T, Bar-Sagi D (1997) Ras effectors and their role in mitogenesis and oncogenesis. J Mol Med 75:587–593

    Article  CAS  PubMed  Google Scholar 

  7. Davies H, Bignell GR, Cox C et al (2002) Mutations of the BRAF gene in human cancer. Nature 417:949–954

    Article  CAS  PubMed  Google Scholar 

  8. Xing M (2005) BRAF mutation in thyroid cancer. Endocr Relat Cancer 12:245–262

    Article  CAS  PubMed  Google Scholar 

  9. Moretti S, Macchiarulo A, De Falco V et al (2006) Biochemical and molecular characterization of the novel BRAF(V599Ins) mutation detected in a classic papillary thyroid carcinoma. Oncogene 25:4235–4240

    Article  CAS  PubMed  Google Scholar 

  10. Xing M (2005) The T1799A BRAF mutation is not a germline mutation in familial nonmedullary thyroid cancer. Clin Endocrinol (Oxf) 63:263–266

    Article  CAS  Google Scholar 

  11. Puxeddu E, Moretti S, Elisei R et al (2004) BRAF(V599E) mutation is the leading genetic event in adult sporadic papillary thyroid carcinomas. J Clin Endocrinol Metab 89:2414–2420

    Article  CAS  PubMed  Google Scholar 

  12. Chung KW, Yang SK, Lee GK et al (2006) Detection of BRAFV600E mutation on fine needle aspiration specimens of thyroid nodule refines cyto-pathology diagnosis, especially in BRAF600E mutation-prevalent area. Clin Endocrinol (Oxf) 65:660–666

    Article  CAS  Google Scholar 

  13. Kimura ET, Nikiforova MN, Zhu Z, Knauf JA, Nikiforov YE, Fagin JA (2003) 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 63:1454–1457

    CAS  PubMed  Google Scholar 

  14. Kim TY, Kim WB, Rhee YS et al (2006) The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma. Clin Endocrinol (Oxf) 65:364–368

    Article  CAS  Google Scholar 

  15. Kumagai A, Namba H, Saenko VA et al (2004) Low frequency of BRAFT1796A mutations in childhood thyroid carcinomas. J Clin Endocrinol Metab 89:4280–4284

    Article  CAS  PubMed  Google Scholar 

  16. Nikiforova MN, Ciampi R, Salvatore G et al (2004) Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas. Cancer Lett 209:1–6

    Article  CAS  PubMed  Google Scholar 

  17. Adeniran AJ, Zhu Z, Gandhi M et al (2006) Correlation between genetic alterations and microscopic features, clinical manifestations, and prognostic characteristics of thyroid papillary carcinomas. Am J Surg Pathol 30:216–222

    Article  PubMed  Google Scholar 

  18. Trovisco V, Vieira de Castro I, Soares P et al (2004) BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J Pathol 202:247–251

    Article  CAS  PubMed  Google Scholar 

  19. Begum S, Rosenbaum E, Henrique R, Cohen Y, Sidransky D, Westra WH (2004) BRAF mutations in anaplastic thyroid carcinoma: implications for tumor origin, diagnosis and treatment. Mod Pathol 17:1359–1363

    Article  CAS  PubMed  Google Scholar 

  20. Nikiforova MN, Kimura ET, Gandhi M et al (2003) BRAF mutations in thyroid tumors are restricted to papillary carcinomas and anaplastic or poorly differentiated carcinomas arising from papillary carcinomas. J Clin Endocrinol Metab 88:5399–5404

    Article  CAS  PubMed  Google Scholar 

  21. Knauf JA, Ma X, Smith EP et al (2005) Targeted expression of BRAFV600E in thyroid cells of transgenic mice results in papillary thyroid cancers that undergo dedifferentiation. Cancer Res 65:4238–4245

    Article  CAS  PubMed  Google Scholar 

  22. Trovisco V, Soares P, Preto A et al (2005) Type and prevalence of BRAF mutations are closely associated with papillary thyroid carcinoma histotype and patients’ age but not with tumour aggressiveness. Virchows Arch 446:589–595

    Article  CAS  PubMed  Google Scholar 

  23. Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA (2003) High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res 63:4561–4567

    CAS  PubMed  Google Scholar 

  24. Giordano TJ, Kuick R, Thomas DG et al (2005) Molecular classification of papillary thyroid carcinoma: distinct BRAF, RAS, and RET/PTC mutation-specific gene expression profiles discovered by DNA microarray analysis. Oncogene 24:6646–6656

    Article  CAS  PubMed  Google Scholar 

  25. Mitsutake N, Miyagishi M, Mitsutake S et al (2006) BRAF mediates RET/PTC-induced mitogen-activated protein kinase activation in thyroid cells: functional support for requirement of the RET/PTC-RAS-BRAF pathway in papillary thyroid carcinogenesis. Endocrinology 147:1014–1019

    Article  CAS  PubMed  Google Scholar 

  26. Riesco-Eizaguirre G, Gutierrez-Martinez P, Garcia-Cabezas MA, Nistal M, Santisteban P (2006) 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. Endocr Relat Cancer 13:257–269

    Article  CAS  PubMed  Google Scholar 

  27. Durante C, Puxeddu E, Ferretti E et al (2007) BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J Clin Endocrinol Metab 92:2840–2843

    Article  CAS  PubMed  Google Scholar 

  28. Mesa C Jr, Mirza M, Mitsutake N et al (2006) 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. Cancer Res 66:6521–6529

    Article  CAS  PubMed  Google Scholar 

  29. Mulligan LM, Kwok JB, Healey CS et al (1993) Germ-line mutations of the RET proto-oncogene in multiple endocrine neoplasia type 2A. Nature 363:458–460

    Article  CAS  PubMed  Google Scholar 

  30. Fusco A, Grieco M, Santoro M et al (1987) A new oncogene in human thyroid papillary carcinomas and their lymph-nodal metastases. Nature 328:170–172

    Article  CAS  PubMed  Google Scholar 

  31. de Groot JW, Links TP, Plukker JT, Lips CJ, Hofstra RM (2006) RET as a diagnostic and therapeutic target in sporadic and hereditary endocrine tumors. Endocr Rev 27:535–560

    Article  PubMed  Google Scholar 

  32. Santoro M, Chiappetta G, Cerrato A et al (1996) Development of thyroid papillary carcinomas secondary to tissue-specific expression of the RET/PTC1 oncogene in transgenic mice. Oncogene 12:1821–1826

    CAS  PubMed  Google Scholar 

  33. Knauf JA, Kuroda H, Basu S, Fagin JA (2003) RET/PTC-induced dedifferentiation of thyroid cells is mediated through Y1062 signaling through SHC-RAS-MAP kinase. Oncogene 22:4406–4412

    Article  CAS  PubMed  Google Scholar 

  34. Melillo RM, Castellone MD, Guarino V et al (2005) The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J Clin Invest 115:1068–1081

    CAS  PubMed  Google Scholar 

  35. Mitsutake N, Knauf JA, Mitsutake S, Mesa C Jr, Zhang L, Fagin JA (2005) Conditional BRAFV600E expression induces DNA synthesis, apoptosis, dedifferentiation, and chromosomal instability in thyroid PCCL3 cells. Cancer Res 65:2465–2473

    Article  CAS  PubMed  Google Scholar 

  36. Elisei R, Romei C, Vorontsova T et al (2001) 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 86:3211–3216

    Article  CAS  PubMed  Google Scholar 

  37. Tallini G, Santoro M, Helie M et al (1998) 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 4:287–294

    CAS  PubMed  Google Scholar 

  38. Rabes HM, Demidchik EP, Sidorow JD et al (2000) Pattern of radiation-induced RET and NTRK1 rearrangements in 191 post-chernobyl papillary thyroid carcinomas: biological, phenotypic, and clinical implications. Clin Cancer Res 6:1093–1103

    CAS  PubMed  Google Scholar 

  39. Chiappetta G, Toti P, Cetta F et al (2002) The RET/PTC oncogene is frequently activated in oncocytic thyroid tumors (Hurthle cell adenomas and carcinomas), but not in oncocytic hyperplastic lesions. J Clin Endocrinol Metab 87:364–369

    Article  CAS  PubMed  Google Scholar 

  40. Sheils O, Smyth P, Finn S, Sweeney EC, O’Leary JJ (2002) RET/PTC rearrangements in Hashimoto’s thyroiditis. Int J Surg Pathol 10:167–168; author reply 8–9

    Google Scholar 

  41. Sugg SL, Ezzat S, Rosen IB, Freeman JL, Asa SL (1998) Distinct multiple RET/PTC gene rearrangements in multifocal papillary thyroid neoplasia. J Clin Endocrinol Metab 83:4116–4122

    Article  CAS  PubMed  Google Scholar 

  42. Thomas GA, Bunnell H, Cook HA et al (1999) High prevalence of RET/PTC rearrangements in Ukrainian and Belarussian post-Chernobyl thyroid papillary carcinomas: a strong correlation between RET/PTC3 and the solid-follicular variant. J Clin Endocrinol Metab 84:4232–4238

    Article  CAS  PubMed  Google Scholar 

  43. Basolo F, Giannini R, Monaco C et al (2002) Potent mitogenicity of the RET/PTC3 oncogene correlates with its prevalence in tall-cell variant of papillary thyroid carcinoma. Am J Pathol 160:247–254

    CAS  PubMed  Google Scholar 

  44. Nikiforov YE (2008) Thyroid carcinoma: molecular pathways and therapeutic targets. Mod Pathol 21(Suppl 2):S37–S43

    Article  CAS  PubMed  Google Scholar 

  45. Namba H, Rubin SA, Fagin JA (1990) Point mutations of ras oncogenes are an early event in thyroid tumorigenesis. Mol Endocrinol 4:1474–1479

    Article  CAS  PubMed  Google Scholar 

  46. Ezzat S, Zheng L, Kolenda J, Safarian A, Freeman JL, Asa SL (1996) Prevalence of activating ras mutations in morphologically characterized thyroid nodules. Thyroid 6:409–416

    Article  CAS  PubMed  Google Scholar 

  47. Suarez HG, du Villard JA, Severino M et al (1990) Presence of mutations in all three ras genes in human thyroid tumors. Oncogene 5:565–570

    CAS  PubMed  Google Scholar 

  48. Motoi N, Sakamoto A, Yamochi T, Horiuchi H, Motoi T, Machinami R (2000) Role of ras mutation in the progression of thyroid carcinoma of follicular epithelial origin. Pathol Res Pract 196:1–7

    CAS  PubMed  Google Scholar 

  49. Vitagliano D, Portella G, Troncone G et al (2006) Thyroid targeting of the N-ras(Gln61Lys) oncogene in transgenic mice results in follicular tumors that progress to poorly differentiated carcinomas. Oncogene 25:5467–5474

    Article  CAS  PubMed  Google Scholar 

  50. Garcia-Rostan G, Zhao H, Camp RL et al (2003) Ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J Clin Oncol 21:3226–3235

    Article  CAS  PubMed  Google Scholar 

  51. Goretzki PE, Lyons J, Stacy-Phipps S et al (1992) Mutational activation of RAS and GSP oncogenes in differentiated thyroid cancer and their biological implications. World J Surg 16:576–581; discussion 81–82

    Google Scholar 

  52. Bongarzone I, Vigneri P, Mariani L, Collini P, Pilotti S, Pierotti MA (1998) RET/NTRK1 rearrangements in thyroid gland tumors of the papillary carcinoma family: correlation with clinicopathological features. Clin Cancer Res 4:223–228

    CAS  PubMed  Google Scholar 

  53. Kroll TG, Sarraf P, Pecciarini L et al (2000) PAX8-PPARgamma1 fusion oncogene in human thyroid carcinoma [corrected]. Science 289:1357–1360

    Article  CAS  PubMed  Google Scholar 

  54. Nikiforova MN, Biddinger PW, Caudill CM, Kroll TG, Nikiforov YE (2002) PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses. Am J Surg Pathol 26:1016–1023

    Article  PubMed  Google Scholar 

  55. Gregory Powell J, Wang X, Allard BL et al (2004) The PAX8/PPARgamma fusion oncoprotein transforms immortalized human thyrocytes through a mechanism probably involving wild-type PPARgamma inhibition. Oncogene 23:3634–3641

    Article  CAS  PubMed  Google Scholar 

  56. Reddi HV, McIver B, Grebe SK, Eberhardt NL (2007) The paired box-8/peroxisome proliferator-activated receptor-gamma oncogene in thyroid tumorigenesis. Endocrinology 148:932–935

    Article  CAS  PubMed  Google Scholar 

  57. Olivier M, Eeles R, Hollstein M, Khan MA, Harris CC, Hainaut P (2002) The IARC TP53 database: new online mutation analysis and recommendations to users. Hum Mutat 19:607–614

    Article  CAS  PubMed  Google Scholar 

  58. Jossart GH, Epstein HD, Shaver JK et al (1996) Immunocytochemical detection of p53 in human thyroid carcinomas is associated with mutation and immortalization of cell lines. J Clin Endocrinol Metab 81:3498–3504

    Article  CAS  PubMed  Google Scholar 

  59. Malaguarnera R, Vella V, Vigneri R, Frasca F (2007) p53 family proteins in thyroid cancer. Endocr Relat Cancer 14:43–60

    Article  CAS  PubMed  Google Scholar 

  60. Jones PA, Baylin SB (2007) The epigenomics of cancer. Cell 128:683–692

    Article  CAS  PubMed  Google Scholar 

  61. Kondo T, Asa SL, Ezzat S (2008) Epigenetic dysregulation in thyroid neoplasia. Endocrinol Metab Clin North Am 37:389–400, ix

    Google Scholar 

  62. Khoo ML, Beasley NJ, Ezzat S, Freeman JL, Asa SL (2002) Overexpression of cyclin D1 and underexpression of p27 predict lymph node metastases in papillary thyroid carcinoma. J Clin Endocrinol Metab 87:1814–1818

    Article  CAS  PubMed  Google Scholar 

  63. Elisei R, Shiohara M, Koeffler HP, Fagin JA (1998) Genetic and epigenetic alterations of the cyclin-dependent kinase inhibitors p15INK4b and p16INK4a in human thyroid carcinoma cell lines and primary thyroid carcinomas. Cancer 83:2185–2193

    Article  CAS  PubMed  Google Scholar 

  64. Schagdarsurengin U, Gimm O, Hoang-Vu C, Dralle H, Pfeifer GP, Dammann R (2002) Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma. Cancer Res 62:3698–3701

    CAS  PubMed  Google Scholar 

  65. Xing M, Cohen Y, Mambo E et al (2004) Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res 64:1664–1668

    Article  CAS  PubMed  Google Scholar 

  66. Kondo T, Zheng L, Liu W, Kurebayashi J, Asa SL, Ezzat S (2007) Epigenetically controlled fibroblast growth factor receptor 2 signaling imposes on the RAS/BRAF/mitogen-activated protein kinase pathway to modulate thyroid cancer progression. Cancer Res 67:5461–5470

    Article  CAS  PubMed  Google Scholar 

  67. Rocha AS, Soares P, Seruca R et al (2001) Abnormalities of the E-cadherin/catenin adhesion complex in classical papillary thyroid carcinoma and in its diffuse sclerosing variant. J Pathol 194:358–366

    Article  CAS  PubMed  Google Scholar 

  68. Xing M, Tokumaru Y, Wu G, Westra WB, Ladenson PW, Sidransky D (2003) Hypermethylation of the Pendred syndrome gene SLC26A4 is an early event in thyroid tumorigenesis. Cancer Res 63:2312–2315

    CAS  PubMed  Google Scholar 

  69. Neumann S, Schuchardt K, Reske A, Emmrich P, Paschke R (2004) Lack of correlation for sodium iodide symporter mRNA and protein expression and analysis of sodium iodide symporter promoter methylation in benign cold thyroid nodules. Thyroid 14:99–111

    Article  CAS  PubMed  Google Scholar 

  70. Venkataraman GM, Yatin M, Marcinek R, Ain KB (1999) Restoration of iodide uptake in dedifferentiated thyroid carcinoma: relationship to human Na+/I-symporter gene methylation status. J Clin Endocrinol Metab 84:2449–2457

    Article  CAS  PubMed  Google Scholar 

  71. Hu S, Liu D, Tufano RP et al (2006) Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer. Int J Cancer 119:2322–2329

    Article  CAS  PubMed  Google Scholar 

  72. Alvarez-Nunez F, Bussaglia E, Mauricio D et al (2006) PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid 16:17–23

    Article  CAS  PubMed  Google Scholar 

  73. Pfeifer GP, Dammann R (2005) Methylation of the tumor suppressor gene RASSF1A in human tumors. Biochemistry (Mosc) 70:576–583

    Article  CAS  Google Scholar 

  74. Milkovic M, Sarcevic B, Glavan E (2006) Expression of MAGE tumor-associated antigen in thyroid carcinomas. Endocr Pathol 17:45–52

    Article  PubMed  Google Scholar 

  75. Feinberg AP, Tycko B (2004) The history of cancer epigenetics. Nat Rev Cancer 4:143–153

    Article  CAS  PubMed  Google Scholar 

  76. Cras A, Darsin-Bettinger D, Balitrand N et al (2007) Epigenetic patterns of the retinoic acid receptor beta2 promoter in retinoic acid-resistant thyroid cancer cells. Oncogene 26:4018–4024

    Article  CAS  PubMed  Google Scholar 

  77. Furuya F, Shimura H, Suzuki H et al (2004) Histone deacetylase inhibitors restore radioiodide uptake and retention in poorly differentiated and anaplastic thyroid cancer cells by expression of the sodium/iodide symporter thyroperoxidase and thyroglobulin. Endocrinology 145:2865–2875

    Article  CAS  PubMed  Google Scholar 

  78. Sansam CG, Roberts CW (2006) Epigenetics and cancer: altered chromatin remodeling via Snf5 loss leads to aberrant cell cycle regulation. Cell Cycle 5:621–624

    Article  CAS  PubMed  Google Scholar 

  79. Thomas D, Friedman S, Lin RY (2008) Thyroid stem cells: lessons from normal development and thyroid cancer. Endocr Relat Cancer 15:51–58

    Article  CAS  PubMed  Google Scholar 

  80. Mitsutake N, Iwao A, Nagai K et al (2007) Characterization of side population in thyroid cancer cell lines: cancer stem-like cells are enriched partly but not exclusively. Endocrinology 148:1797–1803

    Article  CAS  PubMed  Google Scholar 

  81. Zhang P, Zuo H, Ozaki T, Nakagomi N, Kakudo K (2006) Cancer stem cell hypothesis in thyroid cancer. Pathol Int 56:485–489

    Article  CAS  PubMed  Google Scholar 

  82. Salvatore G, Giannini R, Faviana P et al (2004) Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J Clin Endocrinol Metab 89:5175–5180

    Article  CAS  PubMed  Google Scholar 

  83. Cohen Y, Rosenbaum E, Clark DP et al (2004) Mutational analysis of BRAF in fine needle aspiration biopsies of the thyroid: a potential application for the preoperative assessment of thyroid nodules. Clin Cancer Res 10:2761–2765

    Article  CAS  PubMed  Google Scholar 

  84. Rowe LR, Bentz BG, Bentz JS (2006) Utility of BRAF V600E mutation detection in cytologically indeterminate thyroid nodules. Cytojournal 3:10

    Article  PubMed  Google Scholar 

  85. Jin L, Sebo TJ, Nakamura N et al (2006) BRAF mutation analysis in fine needle aspiration (FNA) cytology of the thyroid. Diagn Mol Pathol 15:136–143

    Article  CAS  PubMed  Google Scholar 

  86. Sapio MR, Posca D, Raggioli A et al (2007) Detection of RET/PTC, TRK and BRAF mutations in preoperative diagnosis of thyroid nodules with indeterminate cytological findings. Clin Endocrinol (Oxf) 66:678–683

    Article  CAS  Google Scholar 

  87. Barden CB, Shister KW, Zhu B et al (2003) Classification of follicular thyroid tumors by molecular signature: results of gene profiling. Clin Cancer Res 9:1792–1800

    CAS  PubMed  Google Scholar 

  88. Finley DJ, Zhu B, Barden CB, Fahey TJ 3rd (2004) Discrimination of benign and malignant thyroid nodules by molecular profiling. Ann Surg 240:425–436 discussion 36–37

    Article  PubMed  Google Scholar 

  89. Mazzanti C, Zeiger MA, Costouros NG et al (2004) Using gene expression profiling to differentiate benign versus malignant thyroid tumors. Cancer Res 64:2898–2903

    Article  CAS  PubMed  Google Scholar 

  90. Weber F, Shen L, Aldred MA et al (2005) Genetic classification of benign and malignant thyroid follicular neoplasia based on a three-gene combination. J Clin Endocrinol Metab 90:2512–2521

    Article  CAS  PubMed  Google Scholar 

  91. Kebebew E, Peng M, Reiff E, McMillan A (2006) Diagnostic and extent of disease multigene assay for malignant thyroid neoplasms. Cancer 106:2592–2597

    Article  PubMed  Google Scholar 

  92. Kundra P, Burman KD (2007) Thyroid cancer molecular signaling pathways and use of targeted therapy. Endocrinol Metab Clin North Am 36:839–853, viii

    Google Scholar 

  93. Wilhelm SM, Carter C, Tang L et al (2004) BAY 43–9006 exhibits broad spectrum oral antitumor activity and targets the RAF/MEK/ERK pathway and receptor tyrosine kinases involved in tumor progression and angiogenesis. Cancer Res 64:7099–7109

    Article  CAS  PubMed  Google Scholar 

  94. Ng R, Chen EX (2006) Sorafenib (BAY 43–9006): review of clinical development. Curr Clin Pharmacol 1:223–228

    Article  CAS  PubMed  Google Scholar 

  95. Salvatore G, De Falco V, Salerno P et al (2006) BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin Cancer Res 12:1623–1629

    Article  CAS  PubMed  Google Scholar 

  96. Gupta-Abramson V, Troxel AB, Nellore A et al (2008) Phase II trial of sorafenib in advanced thyroid cancer. J Clin Oncol 26(29):4714–4719

    Google Scholar 

  97. Carlomagno F, Vitagliano D, Guida T et al (2002) ZD6474, an orally available inhibitor of KDR tyrosine kinase activity, efficiently blocks oncogenic RET kinases. Cancer Res 62:7284–7290

    CAS  PubMed  Google Scholar 

  98. Herbst RS, Heymach JV, O’Reilly MS, Onn A, Ryan AJ (2007) Vandetanib (ZD6474): an orally available receptor tyrosine kinase inhibitor that selectively targets pathways critical for tumor growth and angiogenesis. Expert Opin Investig Drugs 16:239–249

    Article  CAS  PubMed  Google Scholar 

  99. Kim DW, Jo YS, Jung HS et al (2006) An orally administered multitarget tyrosine kinase inhibitor, SU11248, is a novel potent inhibitor of thyroid oncogenic RET/papillary thyroid cancer kinases. J Clin Endocrinol Metab 91:4070–4076

    Article  CAS  PubMed  Google Scholar 

  100. Wong E, Rosen LS, Mulay M et al (2007) Sunitinib induces hypothyroidism in advanced cancer patients and may inhibit thyroid peroxidase activity. Thyroid 17:351–355

    Article  CAS  PubMed  Google Scholar 

  101. Ohta K, Endo T, Haraguchi K, Hershman JM, Onaya T (2001) Ligands for peroxisome proliferator-activated receptor gamma inhibit growth and induce apoptosis of human papillary thyroid carcinoma cells. J Clin Endocrinol Metab 86:2170–2177

    Article  CAS  PubMed  Google Scholar 

  102. Martelli ML, Iuliano R, Le Pera I et al (2002) Inhibitory effects of peroxisome poliferator-activated receptor gamma on thyroid carcinoma cell growth. J Clin Endocrinol Metab 87:4728–4735

    Article  CAS  PubMed  Google Scholar 

  103. Park JW, Zarnegar R, Kanauchi H et al (2005) Troglitazone, the peroxisome proliferator-activated receptor-gamma agonist, induces antiproliferation and redifferentiation in human thyroid cancer cell lines. Thyroid 15:222–231

    Article  CAS  PubMed  Google Scholar 

  104. Zarnegar R, Brunaud L, Kanauchi H et al (2002) Increasing the effectiveness of radioactive iodine therapy in the treatment of thyroid cancer using Trichostatin A, a histone deacetylase inhibitor. Surgery 132:984–990; discussion 90

    Google Scholar 

  105. Wischnewski F, Pantel K, Schwarzenbach H (2006) Promoter demethylation and histone acetylation mediate gene expression of MAGE-A1, -A2, -A3, and -A12 in human cancer cells. Mol Cancer Res 4:339–349

    Article  CAS  PubMed  Google Scholar 

  106. Mitsiades CS, Poulaki V, McMullan C et al (2005) Novel histone deacetylase inhibitors in the treatment of thyroid cancer. Clin Cancer Res 11:3958–3965

    Article  CAS  PubMed  Google Scholar 

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Suh, I., Kebebew, E. (2010). The Biology of Thyroid Oncogenesis. In: Sturgeon, C. (eds) Endocrine Neoplasia. Cancer Treatment and Research, vol 153. Springer, Boston, MA. https://doi.org/10.1007/978-1-4419-0857-5_1

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