Mutation Profile of Well-Differentiated Thyroid Cancer in Asians

다국어 초록 (Multilingual Abstract)

Recent advances in molecular diagnostics have led to significant insights into the genetic basis of thyroid tumorigenesis. Among the mutations commonly seen in thyroid cancers, the vast majority are associated with the mitogen-activated protein kinase pathway. B-Raf proto-oncogene (BRAF) mutations are the most common mutations observed in papillary thyroid cancers (PTCs), followed by RET/PTC rearrangements and RAS mutations, while follicular thyroid cancers are more likely to harbor RAS mutations or PAX8/peroxisome proliferator-activated receptor γ (PPARγ) rearrangements. Beyond these more common mutations, alterations in the telomerase reverse transcriptase (TERT) promoter have recently been associated with clinicopathologic features, disease prognosis, and tumorigenesis in thyroid cancer. While the mutations underlying thyroid tumorigenesis are well known, the frequency of these mutations is strongly associated with geography, with clear differences reported between Asian and Western countries. Of particular interest is the prevalence of BRAF mutations, with Korean patients exhibiting the highest rate of BRAF-associated thyroid cancers in the world. Here, we review the prevalence of each of the most common mutations in Asian and Western countries, and identify the characteristics of well-differentiated thyroid cancer in Asians.

참고문헌 (Reference)

1 김혜정, "한국인 갑상선 여포종양의 RAS 변이와 PAX8/PPARγ 재배열의 빈도" 대한내분비학회 27 (27): 45-53, 2012

2 Di Cristofaro J, "ret/PTC1 and ret/PTC3 in thyroid tumors from Chernobyl liquidators: comparison with sporadic tumors from Ukrainian and French patients" 12 : 173-183, 2005

3 Motomura T, "ret rearrangements in Japanese pediatric and adult papillary thyroid cancers" 8 : 485-489, 1998

4 Garcia-Rostan G, "ras mutations are associated with aggressive tumor phenotypes and poor prognosis in thyroid cancer" 21 : 3226-3235, 2003

5 Murray CW, "US Food and Drug Administration’s Total Diet Study: dietary intake of perchlorate and iodine" 18 : 571-580, 2008

6 Park JW, "Troglitazone, the peroxisome proliferator-activated receptor-gamma agonist, induces antiproliferation and redifferentiation in human thyroid cancer cell lines" 15 : 222-231, 2005

7 Jung CK, "The role of TERT promoter mutations and ALK rearrangement in thyroid cancer patients with a high prevalence of the BRAF V600E mutation" 2015

8 Fenton CL, "The ret/PTC mutations are common in sporadic papillary thyroid carcinoma of children and young adults" 85 : 1170-1175, 2000

9 Takahashi K, "The presence of BRAF point mutation in adult papillary thyroid carcinomas from atomic bomb survivors correlates with radiation dose" 46 : 242-248, 2007

10 Riesco-Eizaguirre G, "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" 13 : 257-269, 2006

11 Jung CK, "The increase in thyroid cancer incidence during the last four decades is accompanied by a high frequency of BRAF mutations and a sharp increase in RAS mutations" 99 : E276-E285, 2014

12 Nakabashi CC, "The expression of PAX8-PPARgamma rearrangements is not specific to follicular thyroid carcinoma" 61 : 280-282, 2004

13 Song YS, "The effects of TERT promoter mutation and coexisting mutations on poor outcome in thyroid cancer" 2015

14 Fukahori M, "The associations between RAS mutations and clinical characteristics in follicular thyroid tumors: new insights from a single center and a large patient cohort" 22 : 683-689, 2012

15 Liu T, "The age- and shorter telomere-dependent TERT promoter mutation in follicular thyroid cell-derived carcinomas" 33 : 4978-4984, 2014

16 홍아람, "The Frequency and Clinical Implications of the BRAFV600E Mutation in Papillary Thyroid Cancer Patients in Korea Over the Past Two Decades" 대한내분비학회 29 (29): 505-513, 2014

17 Kim TY, "The BRAF mutation is not associated with poor prognostic factors in Korean patients with conventional papillary thyroid microcarcinoma" 63 : 588-593, 2005

18 Muzza M, "Telomerase in differentiated thyroid cancer: promoter mutations, expression and localization" 399 : 288-295, 2015

19 Gandolfi G, "TERT promoter mutations are associated with distant metastases in papillary thyroid carcinoma" 172 : 403-413, 2015

20 Melo M, "TERT promoter mutations are a major indicator of poor outcome in differentiated thyroid carcinomas" 99 : E754-E765, 2014

21 Liu X, "TERT promoter mutations and their association with BRAF V600E mutation and aggressive clinicopathological characteristics of thyroid cancer" 99 : E1130-E1136, 2014

22 Wang N, "TERT promoter mutation as an early genetic event activating telomerase in follicular thyroid adenoma (FTA) and atypical FTA" 120 : 2965-2979, 2014

23 Vasko V, "Specific pattern of RAS oncogene mutations in follicular thyroid tumors" 88 : 2745-2752, 2003

24 Kim NW, "Specific association of human telomerase activity with immortal cells and cancer" 266 : 2011-2015, 1994

25 Liu RT, "Selective occurrence of ras mutations in benign and malignant thyroid follicular neoplasms in Taiwan" 14 : 616-621, 2004

26 Expert Group on Vitamins and Minerals, "Safe upper levels for vitamins and minerals"

27 Seo Ki Kim, "Role of BRAF V600E mutation as an indicator of the extent of thyroidectomy and lymph node dissection in conventional papillary thyroid carcinoma" Elsevier BV 158 (158): 1500-1511, 2015

28 Puxeddu E, "Ret/PTC activation does not influence clinical and pathological features of adult papillary thyroid carcinomas" 148 : 505-513, 2003

29 Lam AK, "Ret oncogene activation in papillary thyroid carcinoma: prevalence and implication on the histological parameters" 29 : 565-568, 1998

30 Rhoden KJ, "Real-time quantitative RT-PCR identifies distinct c-RET, RET/PTC1 and RET/PTC3 expression patterns in papillary thyroid carcinoma" 84 : 1557-1570, 2004

31 Elisei R, "RET/PTC rearrangements in thyroid nodules: studies in irradiated and not irradiated, malignant and benign thyroid lesions in children and adults" 86 : 3211-3216, 2001

32 Tallini G, "RET/PTC oncogene activation defines a subset of papillary thyroid carcinomas lacking evidence of progression to poorly differentiated or undifferentiated tumor phenotypes" 4 : 287-294, 1998

33 Nibu K, "RET/PTC fusion gene rearrangements in Japanese thyroid carcinomas" 262 : 368-373, 2005

34 Cinti R, "RET rearrangements in papillary thyroid carcinomas and adenomas detected by interphase FISH" 88 : 56-61, 2000

35 Nikiforova MN, "RAS point mutations and PAX8-PPAR gamma rearrangement in thyroid tumors: evidence for distinct molecular pathways in thyroid follicular carcinoma" 88 : 2318-2326, 2003

36 Xing M, "Prognostic utility of BRAF mutation in papillary thyroid cancer" 321 : 86-93, 2010

37 Musholt TJ, "Prognostic significance of RET and NTRK1 rearrangements in sporadic papillary thyroid carcinoma" 128 : 984-993, 2000

38 Park KY, "Prevalences of Gs alpha, ras, p53 mutations and ret/PTC rearrangement in differentiated thyroid tumours in a Korean population" 49 : 317-323, 1998

39 Esapa CT, "Prevalence of Ras mutations in thyroid neoplasia" 50 : 529-535, 1999

40 Zhu Z, "Prevalence of RET/PTC rearrangements in thyroid papillary carcinomas: effects of the detection methods and genetic heterogeneity" 91 : 3603-3610, 2006

41 Namba H, "Point mutations of ras oncogenes are an early event in thyroid tumorigenesis" 4 : 1474-1479, 1990

42 Aiello A, "Peroxisomal proliferator-activated receptor-gamma agonists induce partial reversion of epithelial-mesenchymal transition in anaplastic thyroid cancer cells" 147 : 4463-4475, 2006

43 Sahin M, "PPARgamma staining as a surrogate for PAX8/PPARgamma fusion oncogene expression in follicular neoplasms: clinicopathological correlation and histopathological diagnostic value" 90 : 463-468, 2005

44 Castro P, "PAX8-PPARgamma rearrangement is frequently detected in the follicular variant of papillary thyroid carcinoma" 91 : 213-220, 2006

45 Nikiforova MN, "PAX8-PPARgamma rearrangement in thyroid tumors: RT-PCR and immunohistochemical analyses" 26 : 1016-1023, 2002

46 Scientific Committee on Food, "Opinion of the scientific committee on food on the tolerable upper intake level of iodine" European Commission, Health & Consumer Protection Directorate-General 2002

47 Sugg SL, "Oncogene profile of papillary thyroid carcinoma" 125 : 46-52, 1999

48 Liu RT, "No correlation between BRAFV600E mutation and clinicopathological features of papillary thyroid carcinomas in Taiwan" 63 : 461-466, 2005

49 Jang EK, "NRAS codon 61 mutation is associated with distant metastasis in patients with follicular thyroid carcinoma" 24 : 1275-1281, 2014

50 Basolo F, "N-ras mutation in poorly differentiated thyroid carcinomas: correlation with bone metastases and inverse correlation to thyroglobulin expression" 10 : 19-23, 2000

51 Zhu Z, "Molecular profile and clinical-pathologic features of the follicular variant of papillary thyroid carcinoma. An unusually high prevalence of ras mutations" 120 : 71-77, 2003

52 Rivera M, "Molecular genotyping of papillary thyroid carcinoma follicular variant according to its histological subtypes (encapsulated vs infiltrative) reveals distinct BRAF and RAS mutation patterns" 23 : 1191-1200, 2010

53 Lee SR, "Molecular genotyping of follicular variant of papillary thyroid carcinoma correlates with diagnostic category of fine-needle aspiration cytology: values of RAS mutation testing" 23 : 1416-1422, 2013

54 Di Cristofaro J, "Molecular genetic study comparing follicular variant versus classic papillary thyroid carcinomas: association of N-ras mutation in codon 61 with follicular variant" 37 : 824-830, 2006

55 Kim J, "Lymphatic mapping establishes the role of BRAF gene mutation in papillary thyroid carcinoma" 244 : 799-804, 2006

56 Wajjwalku W, "Low frequency of rearrangements of the ret and trk proto-oncogenes in Japanese thyroid papillary carcinomas" 83 : 671-675, 1992

57 Namba H, "Lack of PTC gene (ret proto-oncogene rearrangement) in human thyroid tumors" 38 : 627-632, 1991

58 Hibi Y, "Is thyroid follicular cancer in Japanese caused by a specific t(2; 3)(q13; p25) translocation generating Pax8-PPAR gamma fusion mRNA?" 51 : 361-366, 2004

59 Dwight T, "Involvement of the PAX8/peroxisome proliferator-activated receptor gamma rearrangement in follicular thyroid tumors" 88 : 4440-4445, 2003

60 Jo YS, "Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer" 91 : 3667-3670, 2006

61 Guo HQ, "Impact of molecular testing in the diagnosis of thyroid fine needle aspiration cytology: data from mainland China" 2014 : 912182-, 2014

62 Liu X, "Highly prevalent TERT promoter mutations in aggressive thyroid cancers" 20 : 603-610, 2013

63 Kang DY, "High prevalence of RET, RAS, and ERK expression in Hashimoto’s thyroiditis and in papillary thyroid carcinoma in the Korean population" 17 : 1031-1038, 2007

64 Oler G, "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" 115 : 972-980, 2009

65 Lee CH, "High frequency of rearrangement of the RET protooncogene (RET/PTC) in Chinese papillary thyroid carcinomas" 83 : 1629-1632, 1998

66 Lemoine NR, "High frequency of ras oncogene activation in all stages of human thyroid tumorigenesis" 4 : 159-164, 1989

67 French CA, "Genetic and biological subgroups of low-stage follicular thyroid cancer" 162 : 1053-1060, 2003

68 Lacroix L, "Follicular thyroid tumors with the PAX8-PPARgamma1 rearrangement display characteristic genetic alterations" 167 : 223-231, 2005

69 Di Cristofaro J, "Expression of tpo mRNA in thyroid tumors: quantitative PCR analysis and correlation with alterations of ret, Braf, ras and pax8 genes" 13 : 485-495, 2006

70 Mayr B, "Expression of Ret/PTC1, -2, -3, -delta3 and -4 in German papillary thyroid carcinoma" 77 : 903-906, 1998

71 Kim KW, "Elevated risk of papillary thyroid cancer in Korean patients with Hashimoto’s thyroiditis" 33 : 691-695, 2011

72 Nikiforov YE, "Distinct pattern of ret oncogene rearrangements in morphological variants of radiation-induced and sporadic thyroid papillary carcinomas in children" 57 : 1690-1694, 1997

73 Naito H, "Different ras gene mutational frequencies in thyroid papillary carcinomas in Japan and Thailand" 131 : 171-175, 1998

74 Ministry of Health, Labour and Welfare, "Dietary reference intakes for Japanese"

75 Kim JY, "Dietary iodine intake and urinary iodine excretion in normal Korean adults" 39 : 355-362, 1998

76 Boos LA, "Diagnostic and prognostic implications of the PAX8-PPARgamma translocation in thyroid carcinomas-a TMA-based study of 226 cases" 63 : 234-241, 2013

77 Musholt TJ, "Detection of papillary thyroid carcinoma by analysis of BRAF and RET/PTC1 mutations in fine-needle aspiration biopsies of thyroid nodules" 34 : 2595-2603, 2010

78 Chung JH, "Detection of RET/PTC oncogene rearrangements in Korean papillary thyroid carcinomas" 9 : 1237-1243, 1999

79 Giordano TJ, "Delineation, functional validation, and bioinformatic evaluation of gene expression in thyroid follicular carcinomas with the PAX8-PPARG translocation" 12 (12): 1983-1993, 2006

80 Basolo F, "Correlation between the BRAF V600E mutation and tumor invasiveness in papillary thyroid carcinomas smaller than 20 millimeters: analysis of 1060 cases" 95 : 4197-4205, 2010

81 Kim SK, "Clinical and pathological features and the BRAF(V600E) mutation in patients with papillary thyroid carcinoma with and without concurrent Hashimoto thyroiditis" 19 : 137-141, 2009

82 Sykorova V, "BRAFV600E mutation in the pathogenesis of a large series of papillary thyroid carcinoma in Czech Republic" 33 : 318-324, 2010

83 Frasca F, "BRAF(V600E) mutation and the biology of papillary thyroid cancer" 15 : 191-205, 2008

84 Ito Y, "BRAF(V600E) mutation analysis in papillary thyroid carcinoma: is it useful for all patients?" 38 : 679-687, 2014

85 Ito Y, "BRAF mutation in papillary thyroid carcinoma in a Japanese population: its lack of correlation with high-risk clinicopathological features and disease-free survival of patients" 56 : 89-97, 2009

86 Park JY, "BRAF and RAS mutations in follicular variants of papillary thyroid carcinoma" 24 : 69-76, 2013

87 Goutas N, "BRAF and K-RAS mutation in a Greek papillary and medullary thyroid carcinoma cohort" 28 (28): 305-308, 2008

88 Xing M, "BRAF V600E and TERT promoter mutations cooperatively identify the most aggressive papillary thyroid cancer with highest recurrence" 32 : 2718-2726, 2014

89 Sahpaz A, "BRAF (V600E) mutation, RET/PTC1 and PAX8-PPAR gamma rearrangements in follicular epithelium derived thyroid lesions: institutional experience and literature review" 32 : 156-166, 2015

90 Guan H, "Association of high iodine intake with the T1799A BRAF mutation in papillary thyroid cancer" 94 : 1612-1617, 2009

91 Liu S, "Association of BRAFV600E mutation with clinicopathological features of papillary thyroid carcinoma: a study on a Chinese population" 7 : 6922-6928, 2014

92 Lupi C, "Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma" 92 : 4085-4090, 2007

93 Lu J, "Association between BRAF V600E mutation and regional lymph node metastasis in papillary thyroid carcinoma" 8 : 793-799, 2015

94 Xing M, "Association between BRAF V600E mutation and mortality in patients with papillary thyroid cancer" 309 : 1493-1501, 2013

95 Jeong SH, "Analysis of RAS mutation and PAX8/PPARgamma rearrangements in follicular-derived thyroid neoplasms in a Korean population: frequency and ultrasound findings" 38 : 849-857, 2015

96 Ishizaka Y, "Activation of the ret-II oncogene without a sequence encoding a transmembrane domain and transforming activity of two ret-II oncogene products differing in carboxy-termini dueto alternative splicing" 4 : 789-794, 1989

97 Kikuchi Y, "Aberrantly methylated genes in human papillary thyroid cancer and their association with BRAF/RAS mutation" 4 : 271-, 2013