28
Views
0
CrossRef citations to date
0
Altmetric
Review

BRAFV600E mutation in papillary thyroid carcinoma: a potential target for therapy?

, &
Pages 467-480 | Published online: 10 Jan 2014

References

  • Ries LAG, Harkins D, Krapcho M et al.SEER Cancer Statistics Review. National Cancer Institute 1975–2003 (2006).
  • Rego-Iraeta A, Perez-Mendez LF, Mantinan B, Garcia-Mayor RV. Time trends for thyroid cancer in northwestern Spain: true rise in the incidence of micro and larger forms of papillary thyroid carcinoma. Thyroid19(4), 333–340 (2009).
  • Davies L, Welch HG. Increasing incidence of thyroid cancer in the United States, 1973–2002. JAMA295(18), 2164–2167 (2006).
  • DeLellis RA LR, Heitz PU, Eng C. World Health Organization Classification of Tumours. Pathology and Genetics of Tumours of Endocrine Glands. IARC Press, Lyon France (2004).
  • Trovisco V, Soares P, Preto A et al. 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(6), 589–595 (2005).
  • Trovisco V, Soares P, Soares R et al. A new BRAF gene mutation detected in a case of a solid variant of papillary thyroid carcinoma. Hum. Pathol.36(6), 694–697 (2005).
  • Trovisco V, Vieira DCI, Soares P et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J. Pathol.202(2), 247–251 (2004).
  • Baudin E, Schlumberger M. New therapeutic approaches for metastatic thyroid carcinoma. Lancet Oncol.8(2), 148–156 (2007).
  • Chow SM, Law SC, Chan JK et al. Papillary microcarcinoma of the thyroid-Prognostic significance of lymph node metastasis and multifocality. Cancer98(1), 31–40 (2003).
  • Ivanova R, Soares P, Castro P, Sobrinho-Simoes M. Diffuse (or multinodular) follicular variant of papillary thyroid carcinoma: a clinicopathologic and immunohistochemical analysis of ten cases of an aggressive form of differentiated thyroid carcinoma. Virchows Arch.440(4), 418–424 (2002).
  • LiVolsi V. Surgical Pathology of the Thyroid. WD Saunders, PA, USA (1990).
  • Hay ID, Hutchinson ME, Gonzalez-Losada T et al. Papillary thyroid microcarcinoma: a study of 900 cases observed in a 60-year period. Surgery144(6), 980–987 (2008).
  • Noguchi S, Yamashita H, Uchino S, Watanabe S. Papillary microcarcinoma. World J. Surg.32(5), 747–753 (2008).
  • Rosai J, LiVolsi VA, Sobrinho-Simoes M, Williams ED. Renaming papillary microcarcinoma of the thyroid gland: the Porto proposal. Int. J. Surg. Pathol.11(4), 249–251 (2003).
  • Kim TY, Hong SJ, Kim JM et al. Prognostic parameters for recurrence of papillary thyroid microcarcinoma. BMC Cancer8, 296 (2008).
  • Mazzaferri EL. Managing small thyroid cancers. JAMA295(18), 2179–2182 (2006).
  • Fonseca E, Soares P, Rossi S, Sobrinho-Simoes M. Prognostic factors in thyroid carcinomas. Verh. Dtsch. Ges. Pathol.81, 82–96 (1997).
  • Lin JD, Liou MJ, Chao TC, Weng HF, Ho YS. Prognostic variables of papillary and follicular thyroid carcinoma patients with lymph node metastases and without distant metastases. Endocr. Relat. Cancer6(1), 109–115 (1999).
  • Soares J, Limbert E, Sobrinho-Simoes M. Diffuse sclerosing variant of papillary thyroid carcinoma: a clinicopathologic study of 10 cases. Pathol. Res. Pract.185(2), 200–206 (1989).
  • Wada N, Masudo K, Nakayama H et al. Clinical outcomes in older or younger patients with papillary thyroid carcinoma: impact of lymphadenopathy and patient age. Eur. J. Surg. Oncol.34(2), 202–207 (2008).
  • Lloyd RV, Erickson LA, Casey MB et al. Observer variation in the diagnosis of follicular variant of papillary thyroid carcinoma. Am. J. Surg. Pathol.28(10), 1336–1340 (2004).
  • Elsheikh TM, Asa SL, Chan JK et al. Interobserver and intraobserver variation among experts in the diagnosis of thyroid follicular lesions with borderline nuclear features of papillary carcinoma. Am. J. Clin. Pathol.130(5), 736–744 (2008).
  • Franc B. Observer variation of lesions of the thyroid. Am. J. Surg. Pathol.27(8), 1177–1179 (2003).
  • Castro P, Fonseca E, Magalhaes J, Sobrinho-Simoes M. Follicular, papillary, and ‘hybrid’ carcinomas of the thyroid. Endocr. Pathol.13(4), 313–320 (2002).
  • Rosai J, Zampi G, Carcangiu ML. Papillary carcinoma of the thyroid: a discussion of its several morphologic expressions, with particular emphasis on the follicular variant. Am. J. Surg. Pathol.7(8), 809–817 (1983).
  • Vickery AL Jr, Carcangiu ML, Johannessen JV, Sobrinho-Simoes M. Papillary carcinoma. Semin. Diagn. Pathol.2(2), 90–100 (1985).
  • Liu J, Singh B, Tallini G et al. Follicular variant of papillary thyroid carcinoma: a clinicopathologic study of a problematic entity. Cancer107(6), 1255–1264 (2006).
  • Sobrinho-Simoes M, Preto A, Rocha AS et al. Molecular pathology of well-differentiated thyroid carcinomas. Virchows Arch.447(5), 787–793 (2005).
  • Castro P, Roque L, Magalhaes J, Sobrinho-Simoes M. A subset of the follicular variant of papillary thyroid carcinoma harbors the PAX8-PPARγ translocation. Int. J. Surg. Pathol.13(3), 235–238 (2005).
  • DeLellis RA. Pathology and genetics of thyroid carcinoma. J. Surg. Oncol.94(8), 662–669 (2006).
  • Maximo V, Sobrinho-Simoes M. Hurthle cell tumours of the thyroid: a review with emphasis on mitochondrial abnormalities with clinical relevance. Virchows Arch.437(2), 107–115 (2000).
  • Sobrinho-Simoes M, Maximo V, Rocha AS et al. Intragenic mutations in thyroid cancer. Endocrinol. Metab. Clin. North Am.37(2), 333–362, viii (2008).
  • Evans HL, Vassilopoulou-Sellin R. Follicular and hurthle cell carcinomas of the thyroid: a comparative study. Am. J. Surg. Pathol.22(12), 1512–1520 (1998).
  • da Rocha Dias S, Friedlos F, Light Y et al. Activated B-RAF is an Hsp90 client protein that is targeted by the anticancer drug 17-allylamino-17-demethoxygeldanamycin. Cancer Res.65(23), 10686–10691 (2005).
  • Johannessen JV, Sobrinho-Simoes M, Lindmo T, Tangen KO. The diagnostic value of flow cytometric DNA measurements in selected disorders of the human thyroid. Am. J. Clin. Pathol.77(1), 20–25 (1982).
  • Castro P, Eknaes M, Teixeira MR et al. Adenomas and follicular carcinomas of the thyroid display two major patterns of chromosomal changes. J. Pathol.206(3), 305–311 (2005).
  • Soares P, dos Santos NR, Seruca R, Lothe RA, Sobrinho-Simoes M. Benign and malignant thyroid lesions show instability at microsatellite loci. Eur. J. Cancer33(2), 293–296 (1997).
  • Zhu Z, Ciampi R, Nikiforova MN, Gandhi M, Nikiforov YE. Prevalence of RET/PTC rearrangements in thyroid papillary carcinomas: effects of the detection methods and genetic heterogeneity. J. Clin. Endocrinol. Metab.91(9), 3603–3610 (2006).
  • Fusco A, Chiappetta G, Hui P et al. Assessment of RET/PTC oncogene activation and clonality in thyroid nodules with incomplete morphological evidence of papillary carcinoma: a search for the early precursors of papillary cancer. Am. J. Pathol.160(6), 2157–2167 (2002).
  • Tallini G. Molecular pathobiology of thyroid neoplasms. Endocr. Pathol.13(4), 271–288 (2002).
  • Teng KK, Hempstead BL. Neurotrophins and their receptors: signaling trios in complex biological systems. Cell. Mol. Life Sci.61(1), 35–48 (2004).
  • Ciampi R, Knauf JA, Kerler R et al. Oncogenic AKAP9–BRAF fusion is a novel mechanism of MAPK pathway activation in thyroid cancer. J. Clin. Invest.115(1), 94–101 (2005).
  • Nikiforov YE. RET/PTC rearrangement in thyroid tumors. Endocr. Pathol.13(1), 3–16 (2002).
  • Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat. Rev. Cancer6(4), 292–306 (2006).
  • 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.83(11), 4116–4122 (1998).
  • 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.4(2), 287–294 (1998).
  • Soares P, Fonseca E, Wynford-Thomas D, Sobrinho-Simoes M. Sporadic ret-rearranged papillary carcinoma of the thyroid: a subset of slow growing, less aggressive thyroid neoplasms? J. Pathol.185(1), 71–78 (1998).
  • Thomas GA, Bunnell H, Cook HA et al. 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(11), 4232–4238 (1999).
  • Nikiforov YE, Rowland JM, Bove KE, Monforte-Munoz H, Fagin JA. Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children. Cancer Res.57(9), 1690–1694 (1997).
  • Motomura T, Nikiforov YE, Namba H et al. ret rearrangements in Japanese pediatric and adult papillary thyroid cancers. Thyroid8(6), 485–489 (1998).
  • Williams D. Cancer after nuclear fallout: lessons from the chernobyl accident. Nat. Rev. Cancer2(7), 543–549 (2002).
  • Liu RT, Chen YJ, Chou FF et al. No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan. Clin. Endocrinol. (Oxf.)63(4), 461–466 (2005).
  • Musholt TJ, Musholt PB, Khaladj N et al. Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma. Surgery128(6), 984–993 (2000).
  • Kuo CS, Lin CY, Hsu CW, Lee CH, Lin HD. Low frequency of rearrangement of TRK protooncogene in Chinese thyroid tumors. Endocrine13(3), 341–344 (2000).
  • Bos JL. ras oncogenes in human cancer: a review. Cancer Res.49(17), 4682–4689 (1989).
  • Peyssonnaux C, Eychene A. The Raf/MEK/ERK pathway: new concepts of activation. Biol. Cell.93(1–2), 53–62 (2001).
  • 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.120(1), 71–77 (2003).
  • Vasko V, Ferrand M, Di Cristofaro J et al. Specific pattern of RAS oncogene mutations in follicular thyroid tumors. J. Clin. Endocrinol. Metab.88(6), 2745–2752 (2003).
  • Castro P, Rebocho AP, Soares RJ et al. PAX8-PPARγ rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab.91(1), 213–220 (2006).
  • Di Cristofaro J, Marcy M, Vasko V et al. Molecular genetic study comparing follicular variant versus classic papillary thyroid carcinomas: association of N-ras mutation in codon 61 with follicular variant. Hum. Pathol.37(7), 824–830 (2006).
  • Manenti G, Pilotti S, Re FC, Della Porta G, Pierotti MA. Selective activation of ras oncogenes in follicular and undifferentiated thyroid carcinomas. Eur. J. Cancer30A(7), 987–993 (1994).
  • Soares P, Trovisco V, Rocha AS et al. BRAF mutations and RET/PTC rearrangements are alternative events in the etiopathogenesis of PTC. Oncogene22(29), 4578–4580 (2003).
  • Garcia-Rostan G, Zhao H, Camp RL et al. ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer. J. Clin. Oncol.21(17), 3226–3235 (2003).
  • 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. Thyroid10(1), 19–23 (2000).
  • Costa AM, Herrero A, Fresno MF et al. BRAF mutation associated with other genetic events identifies a subset of aggressive papillary thyroid carcinoma. Clin. Endocrinol. (Oxf.)68(4), 618–634 (2008).
  • Fukushima T, Suzuki S, Mashiko M et al. BRAF mutations in papillary carcinomas of the thyroid. Oncogene22(41), 6455–6457 (2003).
  • Hara H, Fulton N, Yashiro T et al. N-ras mutation: an independent prognostic factor for aggressiveness of papillary thyroid carcinoma. Surgery116(6), 1010–1016 (1994).
  • 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.13(4), 1161–1170 (2007).
  • Wang Y, Hou P, Yu H et al. High prevalence and mutual exclusivity of genetic alterations in the phosphatidylinositol-3-kinase/akt pathway in thyroid tumors. J. Clin. Endocrinol. Metab.92(6), 2387–2390 (2007).
  • Nikiforova MN, Lynch RA, Biddinger PW et al. RAS point mutations and PAX8–PPAR γ rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma. J. Clin. Endocrinol. Metab.88(5), 2318–2326 (2003).
  • Soares P, Berx G, van Roy F, Sobrinho-Simoes M. E-cadherin gene alterations are rare events in thyroid tumors. Int. J. Cancer70(1), 32–38 (1997).
  • Rocha AS, Soares P, Fonseca E et al. E-cadherin loss rather than β-catenin alterations is a common feature of poorly differentiated thyroid carcinomas. Histopathology42(6), 580–587 (2003).
  • Rocha AS, Soares P, Seruca R et al. Abnormalities of the E-cadherin/catenin adhesion complex in classical papillary thyroid carcinoma and in its diffuse sclerosing variant. J. Pathol.194(3), 358–366 (2001).
  • Scarpino S, Cancellario d’Alena F, Di Napoli A et al. Increased expression of Met protein is associated with up-regulation of hypoxia inducible factor-1 (HIF-1) in tumour cells in papillary carcinoma of the thyroid. J. Pathol.202(3), 352–358 (2004).
  • Scarpino S, Stoppacciaro A, Colarossi C et al. Hepatocyte growth factor (HGF) stimulates tumour invasiveness in papillary carcinoma of the thyroid. J. Pathol.189(4), 570–575 (1999).
  • Scarpino S, Duranti E, Stoppacciaro A et al. COX-2 is induced by HGF stimulation in Met-positive thyroid papillary carcinoma cells and is involved in tumour invasiveness. J. Pathol.218(4), 487-494 (2009).
  • Sobrinho-Simoes MA, Nesland JM, Holm R, Sambade MC, Johannessen JV. Hurthle cell and mitochondrion-rich papillary carcinomas of the thyroid gland: an ultrastructural and immunocytochemical study. Ultrastruct. Pathol.8(2–3), 131–142 (1985).
  • Maximo V, Lima J, Soares P, Sobrinho-Simoes M. Mitochondria and cancer. Virchows Arch.454(5), 481–495 (2009).
  • DeBerardinis RJ. Is cancer a disease of abnormal cellular metabolism? New angles on an old idea. Genet. Med.10(11), 767–777 (2008).
  • Beck TW, Huleihel M, Gunnell M, Bonner TI, Rapp UR. The complete coding sequence of the human A-raf-1 oncogene and transforming activity of a human A-raf carrying retrovirus. Nucleic Acids Res.15(2), 595–609 (1987).
  • Bonner TI, Kerby SB, Sutrave P et al. Structure and biological activity of human homologs of the raf/mil oncogene. Mol. Cell. Biol.5(6), 1400–1407 (1985).
  • Huleihel M, Goldsborough M, Cleveland J et al. Characterization of murine A-raf, a new oncogene related to the v-raf oncogene. Mol. Cell. Biol.6(7), 2655–2662 (1986).
  • Ikawa S, Fukui M, Ueyama Y et al. B-raf, a new member of the raf family, is activated by DNA rearrangement. Mol. Cell. Biol.8(6), 2651–2654 (1988).
  • Rapp UR, Goldsborough MD, Mark GE et al. Structure and biological activity of v-raf, a unique oncogene transduced by a retrovirus. Proc. Natl Acad. Sci. USA80(14), 4218–4222 (1983).
  • Storm SM, Cleveland JL, Rapp UR. Expression of raf family proto-oncogenes in normal mouse tissues. Oncogene5(3), 345–351 (1990).
  • Barnier JV, Papin C, Eychene A, Lecoq O, Calothy G. The mouse B-raf gene encodes multiple protein isoforms with tissue-specific expression. J. Biol. Chem.270(40), 23381–23389 (1995).
  • Luckett JC, Huser MB, Giagtzoglou N, Brown JE, Pritchard CA. Expression of the A-raf proto-oncogene in the normal adult and embryonic mouse. Cell Growth Differ.11(3), 163–171 (2000).
  • Wojnowski L, Zimmer AM, Beck TW et al. Endothelial apoptosis in Braf-deficient mice. Nat. Genet.16(3), 293–297 (1997).
  • Wojnowski L, Stancato LF, Larner AC, Rapp UR, Zimmer A. Overlapping and specific functions of Braf and Craf-1 proto-oncogenes during mouse embryogenesis. Mech. Dev.91(1–2), 97–104 (2000).
  • Wellbrock C, Karasarides M, Marais R. The RAF proteins take centre stage. Nat. Rev. Mol. Cell Biol.5(11), 875–885 (2004).
  • Brtva TR, Drugan JK, Ghosh S et al. Two distinct Raf domains mediate interaction with Ras. J. Biol. Chem.270(17), 9809–9812 (1995).
  • Hu CD, Kariya K, Tamada M et al. Cysteine-rich region of Raf-1 interacts with activator domain of post-translationally modified Ha-Ras. J. Biol. Chem.270(51), 30274–30277 (1995).
  • Winkler DG, Cutler RE Jr, Drugan JK et al. Identification of residues in the cysteine-rich domain of Raf-1 that control Ras binding and Raf-1 activity. J. Biol. Chem.273(34), 21578–21584 (1998).
  • Cutler RE Jr, Stephens RM, Saracino MR, Morrison DK. Autoregulation of the Raf-1 serine/threonine kinase. Proc. Natl Acad. Sci. USA95(16), 9214–9219 (1998).
  • Chong H, Guan KL. Regulation of Raf through phosphorylation and N terminus-C terminus interaction. J. Biol. Chem.278(38), 36269–36276 (2003).
  • Tran NH, Frost JA. Phosphorylation of Raf-1 by p21-activated kinase 1 and Src regulates Raf-1 autoinhibition. J. Biol. Chem.278(13), 11221–11226 (2003).
  • Tran NH, Wu X, Frost JA. B-Raf and Raf-1 are regulated by distinct autoregulatory mechanisms. J. Biol. Chem.280(16), 16244–16253 (2005).
  • Terai K, Matsuda M. Ras binding opens c-Raf to expose the docking site for mitogen-activated protein kinase kinase. EMBO Rep.6(3), 251–255 (2005).
  • Kikuchi A, Williams LT. The post-translational modification of ras p21 is important for Raf-1 activation. J. Biol. Chem.269(31), 20054–20059 (1994).
  • Leevers SJ, Paterson HF, Marshall CJ. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane. Nature369(6479), 411–414 (1994).
  • Mineo C, Anderson RG, White MA. Physical association with ras enhances activation of membrane-bound raf (RafCAAX). J. Biol. Chem.272(16), 10345–10348 (1997).
  • Li W, Melnick M, Perrimon N. Dual function of Ras in Raf activation. Development125(24), 4999–5008 (1998).
  • Roux PP, Blenis J. ERK and p38 MAPK-activated protein kinases: a family of protein kinases with diverse biological functions. Microbiol. Mol. Biol. Rev.68(2), 320–344 (2004).
  • Davies H, Bignell GR, Cox C et al. Mutations of the BRAF gene in human cancer. Nature417(6892), 949–954 (2002).
  • Wan PT, Garnett MJ, Roe SM et al. Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF. Cell116(6), 855–867 (2004).
  • Kimura ET, Nikiforova MN, Zhu Z et al. 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(7), 1454–1457 (2003).
  • Cohen Y, Xing M, Mambo E et al. BRAF mutation in papillary thyroid carcinoma. JNCI Cancer Spectrum95(8), 625–627 (2003).
  • Xu X, Quiros RM, Gattuso P, Ain KB, Prinz RA. High prevalence of BRAF gene mutation in papillary thyroid carcinomas and thyroid tumor cell lines. Cancer Res.63(15), 4561–4567 (2003).
  • Namba H, Nakashima M, Hayashi T et al. Clinical implication of hot spot BRAF mutation, V599E, in papillary thyroid cancers. J. Clin. Endocrinol. Metab.88(9), 4393–4397 (2003).
  • Nikiforova MN, Kimura ET, Gandhi M et al. 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(11), 5399–5404 (2003).
  • Lima J, Trovisco V, Soares P et al. BRAF mutations are not a major event in post-chernobyl childhood thyroid carcinomas. J. Clin. Endocrinol. Metab.89(9), 4267–4271 (2004).
  • Kim KH, Suh KS, Kang DW, Kang DY. Mutations of the BRAF gene in papillary thyroid carcinoma and in Hashimoto’s thyroiditis. Pathol. Int.55(9), 540–545 (2005).
  • Ugolini C, Giannini R, Lupi C et al. Presence of BRAF V600E in very early stages of papillary thyroid carcinoma. Thyroid17(5), 381–388 (2007).
  • Soares P, Trovisco V, Rocha AS et al. BRAF mutations typical of papillary thyroid carcinoma are more frequently detected in undifferentiated than in insular and insular-like poorly differentiated carcinomas. Virchows Arch.444(6), 572–576 (2004).
  • Xing M. BRAF mutation in thyroid cancer. Endocr. Relat. Cancer.12(2), 245–262 (2005).
  • Perren A, Schmid S, Locher T et al. BRAF and endocrine tumors: mutations are frequent in papillary thyroid carcinomas, rare in endocrine tumors of the gastrointestinal tract and not detected in other endocrine tumors. Endocr. Relat. Cancer11(4), 855–860 (2004).
  • Trovisco V, Vieira de Castro I, Soares P et al. BRAF mutations are associated with some histological types of papillary thyroid carcinoma. J. Pathol.202(2), 247–251 (2004).
  • Nikiforova MN, Ciampi R, Salvatore G et al. Low prevalence of BRAF mutations in radiation-induced thyroid tumors in contrast to sporadic papillary carcinomas. Cancer Lett.209(1), 1–6 (2004).
  • Kumagai A, Namba H, Saenko VA et al. Low Frequency of BRAFT1796A mutations in childhood thyroid carcinomas. J. Clin. Endocrinol. Metab.89(9), 4280–4284 (2004).
  • Powell N, Jeremiah S, Morishita M et al. Frequency of BRAF T1796A mutation in papillary thyroid carcinoma relates to age of patient at diagnosis and not to radiation exposure. J. Pathol.205(5), 558–564 (2005).
  • Nikiforova MN, Stringer JR, Blough R et al. Proximity of chromosomal loci that participate in radiation-induced rearrangements in human cells. Science290(5489), 138–141 (2000).
  • Sugg SL, Zheng L, Rosen IB et al. ret/PTC-1, -2, and -3 oncogene rearrangements in human thyroid carcinomas: implications for metastatic potential? J. Clin. Endocrinol. Metab.81(9), 3360–3365 (1996).
  • Bongarzone I, Fugazzola L, Vigneri P et al. Age-related activation of the tyrosine kinase receptor protooncogenes RET and NTRK1 in papillary thyroid carcinoma. J. Clin. Endocrinol. Metab.81(5), 2006–2009 (1996).
  • 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.30(2), 216–222 (2006).
  • Williams D, Baverstock K. Chernobyl and the future: too soon for a final diagnosis. Nature440(7087), 993–994 (2006).
  • Fugazzola L, Mannavola D, Cirello V et al. BRAF mutations in an Italian cohort of thyroid cancers. Clin. Endocrinol. (Oxf.)61(2), 239–243 (2004).
  • Cohen Y, Rosenbaum E, Clark DP et al. 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(8), 2761–2765 (2004).
  • Frattini M, Ferrario C, Bressan P et al. Alternative mutations of BRAF, RET and NTRK1 are associated with similar but distinct gene expression patterns in papillary thyroid cancer. Oncogene23(44), 7436–7440 (2004).
  • Salvatore G, Giannini R, Faviana P et al. Analysis of BRAF point mutation and RET/PTC rearrangement refines the fine-needle aspiration diagnosis of papillary thyroid carcinoma. J. Clin. Endocrinol. Metab.89(10), 5175–5180 (2004).
  • Melillo RM, Castellone MD, Guarino V et al. The RET/PTC-RAS-BRAF linear signaling cascade mediates the motile and mitogenic phenotype of thyroid cancer cells. J. Clin. Invest.115(4), 1068–1081 (2005).
  • Mitsutake N, Miyagishi M, Mitsutake S et al. BRAF mediates RET/PTC-induced MAPK activation in thyroid cells: functional support for requirement of the RET/PTC-RAS-BRAF pathway in papillary thyroid carcinogenesis. Endocrinology147(2), 1014-1019 (2005).
  • Kim TY, Kim WB, Song JY et al. The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma. Clin. Endocrinol. (Oxf.)63(5), 588–593 (2005).
  • Kim TY, Kim WB, Rhee YS et al. The BRAF mutation is useful for prediction of clinical recurrence in low-risk patients with conventional papillary thyroid carcinoma. Clin. Endocrinol. (Oxf.)65(3), 364–368 (2006).
  • Xing M, Westra WH, Tufano RP et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J. Clin. Endocrinol. Metab.90(12), 6373–6379 (2005).
  • 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.93(10), 3943–3949 (2008).
  • Xing M, Clark D, Guan H et al. BRAF mutation testing of thyroid fine-needle aspiration biopsy specimens for preoperative risk stratification in papillary thyroid cancer. J. Clin. Oncol.27(18), 2977–2982 (2009).
  • Ricarte-Filho JC, Ryder M, Chitale DA et al. Mutational profile of advanced primary and metastatic radioactive iodine-refractory thyroid cancers reveals distinct pathogenetic roles for BRAF, PIK3CA, and AKT1. Cancer Res.69(11), 4885–4893 (2009).
  • 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.65(10), 4238–4245 (2005).
  • Trovisco V, Couto JP, Cameselle-Teijeiro J et al. Acquisition of BRAF gene mutations is not a requirement for nodal metastasis of papillary thyroid carcinoma. Clin. Endocrinol. (Oxf.)69(4), 683–685 (2008).
  • Couto JP, Prazeres H, Castro P et al. How molecular pathology is changing and will change the therapeutics of patients with follicular cell-derived thyroid cancer? J. Clin. Pathol.62(5), 414-421 (2009).
  • Espinosa AV, Porchia L, Ringel MD. Targeting BRAF in thyroid cancer. Br. J. Cancer96(1), 16–20 (2007).
  • Mitsiades CS, Negri J, McMullan C et al. Targeting BRAFV600E in thyroid carcinoma: therapeutic implications. Mol. Cancer Ther.6(3), 1070–1078 (2007).
  • Durante C, Puxeddu E, Ferretti E et al. BRAF mutations in papillary thyroid carcinomas inhibit genes involved in iodine metabolism. J. Clin. Endocrinol. Metab.92(7), 2840–2843 (2007).
  • 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. Endocr. Relat. Cancer15(2), 511–520 (2008).
  • Liu D, Liu Z, Condouris S, Xing M. BRAF V600E maintains proliferation, transformation, and tumorigenicity of BRAF-mutant papillary thyroid cancer cells. J. Clin. Endocrinol. Metab.92(6), 2264–2271 (2007).
  • 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. Clin. Cancer Res.12(6), 1785–1793 (2006).
  • Salvatore G, De Falco V, Salerno P et al. BRAF is a therapeutic target in aggressive thyroid carcinoma. Clin. Cancer Res.12(5), 1623–1629 (2006).
  • Lyons JF, Wilhelm S, Hibner B, Bollag G. Discovery of a novel Raf kinase inhibitor. Endocr. Relat. Cancer8(3), 219–225 (2001).
  • Wilhelm SM, Carter C, Tang L et al. 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(19), 7099–7109 (2004).
  • Kim S, Yazici YD, Calzada G et al. sorafenib inhibits the angiogenesis and growth of orthotopic anaplastic thyroid carcinoma xenografts in nude mice. Mol. Cancer Ther.6(6), 1785–1792 (2007).
  • Murphy DA, Makonnen S, Lassoued W et al. Inhibition of tumor endothelial ERK activation, angiogenesis, and tumor growth by sorafenib (BAY43–9006). Am. J. Pathol.169(5), 1875–1885 (2006).
  • Henderson YC, Ahn SH, Kang Y, Clayman GL. sorafenib potently inhibits papillary thyroid carcinomas harboring RET/PTC1 rearrangement. Clin. Cancer Res.14(15), 4908–4914 (2008).
  • Gupta-Abramson V, Troxel AB, Nellore A et al. Phase II trial of sorafenib in advanced thyroid cancer. J. Clin. Oncol.26(29), 4714–4719 (2008).
  • Strumberg D, Awada A, Hirte H et al. Pooled safety analysis of BAY 43–9006 (sorafenib) monotherapy in patients with advanced solid tumours: is rash associated with treatment outcome? Eur. J. Cancer42(4), 548–556 (2006).
  • Steeghs N, Nortier JW, Gelderblom H. Small molecule tyrosine kinase inhibitors in the treatment of solid tumors: an update of recent developments. Ann. Surg. Oncol.14(2), 942–953 (2007).
  • Kloos RT, Ringel MD, Knopp MV et al. Phase II trial of sorafenib in metastatic thyroid cancer. J. Clin. Oncol.27(10), 1675–1684 (2009).
  • Beeram M, Patnaik A, Rowinsky EK. Raf: a strategic target for therapeutic development against cancer. J. Clin. Oncol.23(27), 6771–6790 (2005).
  • Gorre ME, Mohammed M, Ellwood K et al. Clinical resistance to STI-571 cancer therapy caused by BCR–ABL gene mutation or amplification. Science293(5531), 876–880 (2001).
  • Mahon FX, Belloc F, Lagarde V et al. MDR1 gene overexpression confers resistance to imatinib mesylate in leukemia cell line models. Blood101(6), 2368–2373 (2003).
  • Pao W, Miller VA, Politi KA et al. Acquired resistance of lung adenocarcinomas to gefitinib or erlotinib is associated with a second mutation in the EGFR kinase domain. PLoS Med.2(3), e73 (2005).
  • Pao W, Wang TY, Riely GJ et al. KRAS mutations and primary resistance of lung adenocarcinomas to gefitinib or erlotinib. PLoS Med.2(1), e17 (2005).
  • Solit DB, Garraway LA, Pratilas CA et al. BRAF mutation predicts sensitivity to MEK inhibition. Nature439(7074), 358–362 (2006).
  • Sebolt-Leopold JS, Dudley DT, Herrera R et al. Blockade of the MAP kinase pathway suppresses growth of colon tumors in vivo. Nat. Med.5(7), 810–816 (1999).
  • Collisson EA, De A, Suzuki H, Gambhir SS, Kolodney MS. Treatment of metastatic melanoma with an orally available inhibitor of the Ras–Raf–MAPK cascade. Cancer Res.63(18), 5669–5673 (2003).
  • Liu D, Liu Z, Jiang D, Dackiw AP, Xing M. Inhibitory effects of the mitogen-activated protein kinase kinase inhibitor CI-1040 on the proliferation and tumor growth of thyroid cancer cells with BRAF or RAS mutations. J. Clin. Endocrinol. Metab.92(12), 4686–4695 (2007).
  • Richly H, Henning BF, Kupsch P et al. Results of a Phase I trial of sorafenib (BAY 43–9006) in combination with doxorubicin in patients with refractory solid tumors. Ann. Oncol.17(5), 866–873 (2006).
  • Takimoto CH, Awada A. Safety and anti-tumor activity of sorafenib (Nexavar) in combination with other anti-cancer agents: a review of clinical trials. Cancer Chemother. Pharmacol.61(4), 535–548 (2008).
  • Lejeune FJ, Rimoldi D, Speiser D. New approaches in metastatic melanoma: biological and molecular targeted therapies. Expert. Rev. Anticancer Ther.7(5), 701–713 (2007).
  • Jaiswal RK, Weissinger E, Kolch W, Landreth GE. Nerve growth factor-mediated activation of the mitogen-activated protein (MAP) kinase cascade involves a signaling complex containing B-Raf and HSP90. J. Biol. Chem.271(39), 23626–23629 (1996).
  • Grbovic OM, Basso AD, Sawai A et al. V600E B-Raf requires the Hsp90 chaperone for stability and is degraded in response to Hsp90 inhibitors. Proc. Natl Acad. Sci. USA103(1), 57–62 (2006).
  • Braga-Basaria M, Ringel MD. Clinical review 158: beyond radioiodine: a review of potential new therapeutic approaches for thyroid cancer. J. Clin. Endocrinol. Metab.88(5), 1947–1960 (2003).
  • 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. Mol. Cancer Res.6(5), 751–759 (2008).
  • Tsai J, Lee JT, Wang W et al. Discovery of a selective inhibitor of oncogenic B-Raf kinase with potent antimelanoma activity. Proc. Natl Acad. Sci. USA105(8), 3041–3046 (2008).
  • Wong H, Belvin M, Herter S et al. Pharmacodynamics of 2-[4-[(1E)-1-(hydroxyimino)-2,3-dihydro-1H-inden-5-yl]-3-(pyridine-4-yl)-1H-pyrazol-1-yl]ethan-1-ol (GDC-0879), a potent and selective B-Raf kinase inhibitor: understanding relationships between systemic concentrations, phosphorylated mitogen-activated protein kinase kinase 1 inhibition, and efficacy. J. Pharmacol. Exp. Ther.329(1), 360–367 (2009).

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.