Journal List > J Korean Thyroid Assoc > v.7(2) > 1056553

TOOLS
Tae, Chi, Kim, Lee, and Youn: Gene Methylation Associated with Differentiated Thyroid Cancer
Review Article

Clin Exp Thyroidol 2014 2014;7(2):118-128.

Published online: 7 November 2014

DOI: https://doi.org/10.11106/cet.2014.7.2.118

Gene Methylation Associated with Differentiated Thyroid Cancer

Soon Young Tae1, Hyun-Keun Chi1, Su-jin Kim1, Kyu Eun Lee1, Yeo-Kyu Youn1, 2

Department of Surgery, Seoul National University Hospital and College of Medicine, Division of Surgery, Thyroid Center, Seoul National University Cancer Center and Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea

Department of Surgery, National Medical Center, Seoul, Korea

This study was supported by the Seoul National University Hospital Research Fund (Grant Number 04-2013-0070).

Correspondence: Kyu Eun Lee, MD, PhD, Cancer Research Institute, Seoul National University College of Medicine, 101 Daehak-ro, Jongno-gu, Seoul 110-744, Korea Tel: 82-2-2072-2018, Fax: 82-2-766-3975, E-mail: kyulee@medimail.co.kr

Received 15 January 2014       Accepted 20 May 2014

Copyright © 2014, the Korean Thyroid Association.

This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/), which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Epigenetic alteration changes expression of many genes, such as tumor suppressor gene and molecular specific gene, without change in DNA sequence. Cancers, including thyroid cancer, often exhibit an aberrant methylation of gene promoter regions, which is associated with loss of gene function. Aberrant methylation plays a fundamental role in tumorigenesis. Methylation of some genes tends to occur in certain types of thyroid cancer. Methylation of TIMP3, SLC5A8, p16, RAR β2, DAPK genes is associated with papillary thyroid cancer. Some studies show that aberrant methylation is related to the BRAF V600E mutation. Methylation of PTEN and RASSF1A genes occurs commonly in follicular thyroid cancer. Methylation of thyroid-specific genes, such as sodium/iodide symporter, thyroid-stimulating hormone receptor, and SLC26A4 which encodes pendrine, also has a relation to thyroid cancer. Methylation of these genes could be utilized as markers to detect early disease, to define prognosis and to predict therapeutic targets of thyroid cancer.

Keywords: Epigenetics, Methylation, Thyroid cancer, Genes, Tumor suppressor

References

1. Feinberg AP, Tycko B. The history of cancer epigenetics. Nat Rev Cancer. 2004; 4(2):143–53.
crossref
2. Herman JG, Baylin SB. Gene silencing in cancer in association with promoter hypermethylation. N Engl J Med. 2003; 349(21):2042–54.
crossref
3. Waddington CH. The epigenotype. 1942. Int J Epidemiol. 2012; 41(1):10–3.
4. Feinberg AP, Vogelstein B. Hypomethylation distinguishes genes of some human cancers from their normal counterparts. Nature. 1983; 301(5895):89–92.
crossref
5. Greger V, Passarge E, Hopping W, Messmer E, Horsthemke B. Epigenetic changes may contribute to the formation and spontaneous regression of retinoblastoma. Hum Genet. 1989; 83(2):155–8.
crossref
6. Xing M. Gene methylation in thyroid tumorigenesis. Endocrinology. 2007; 148(3):948–53.
crossref
7. Bird A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002; 16(1):6–21.
crossref
8. Yoo CB, Jones PA. Epigenetic therapy of cancer: past, present and future. Nat Rev Drug Discov. 2006; 5(1):37–50.
crossref
9. Yokomori N, Tawata M, Saito T, Shimura H, Onaya T. Regulation of the rat thyrotropin receptor gene by the methylation-sensitive transcription factor GA-binding protein. Mol Endocrinol. 1998; 12(8):1241–9.
crossref
10. Reik W, Lewis A. Co-evolution of X-chromosome inactivation and imprinting in mammals. Nat Rev Genet. 2005; 6(5):403–10.
crossref
11. Feinberg AP, Cui H, Ohlsson R. DNA methylation and genomic imprinting: insights from cancer into epigenetic mechanisms. Semin Cancer Biol. 2002; 12(5):389–98.
crossref
12. Feinberg AP, Ohlsson R, Henikoff S. The epigenetic progenitor origin of human cancer. Nat Rev Genet. 2006; 7(1):21–33.
crossref
13. Robertson KD. DNA methylation and chromatin - unraveling the tangled web. Oncogene. 2002; 21(35):5361–79.
crossref
14. Kornberg RD, Lorch Y. Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell. 1999; 98(3):285–94.
crossref
15. Park IS. Epigenetics in head and neck cancer. Korean J Otorhinolaryngol-Head Neck Surg. 2009; 52(12):943–8.
crossref
16. Piperi C, Papavassiliou AG. Strategies for DNA methylation analysis in developmental studies. Dev Growth Differ. 2011; 53(3):287–99.
crossref
17. He L, Hannon GJ. MicroRNAs: small RNAs with a big role in gene regulation. Nat Rev Genet. 2004; 5(7):522–31.
crossref
18. Hundahl SA, Fleming ID, Fremgen AM, Menck HR. A National Cancer Data Base report on 53,856 cases of thyroid carcinoma treated in the U.S., 1985-1995 [see commetns]. Cancer. 1998; 83(12):2638–48.
19. Hu S, Liu D, Tufano RP, Carson KA, Rosenbaum E, Cohen Y. et al. Association of aberrant methylation of tumor suppressor genes with tumor aggressiveness and BRAF mutation in papillary thyroid cancer. Int J Cancer. 2006; 119(10):2322–9.
20. Ko HJ, Kim BY, Jung CH, Chun SW, Mok JO, Kim YJ. et al. DNA methylation of RUNX3 in papillary thyroid cancer. Korean J Intern Med. 2012; 27(4):407–10.
21. Mohammadi-asl J, Larrijani B, Khorgami Z, Tavangar SM, Haghpanah V, Kheirollahi M. et al. Qualitative and quantitative promoter hypermethylation patterns of the P16, TSHR, RASSF1A and RARbeta2 genes in papillary thyroid carcinoma. Med Oncol. 2011; 28(4):1123–8.
22. Porra V, Ferraro-Peyret C, Durand C, Selmi-Ruby S, Giroud H, Berger-Dutrieux N. et al. Silencing of the tumor suppressor gene SLC5A8 is associated with BRAF mutations in classical papillary thyroid carcinomas. J Clin Endocrinol Metab. 2005; 90(5):3028–35.
23. Wang P, Pei R, Lu Z, Rao X, Liu B. Methylation of p16 CpG islands correlated with metastasis and aggressiveness in papillary thyroid carcinoma. J Chin Med Assoc. 2013; 76(3):135–9.
crossref
24. Anania MC, Sensi M, Radaelli E, Miranda C, Vizioli MG, Pagliardini S. et al. TIMP3 regulates migration, invasion and in vivo tumorigenicity of thyroid tumor cells. Oncogene. 2011; 30(27):3011–23.
25. Anand-Apte B, Bao L, Smith R, Iwata K, Olsen BR, Zetter B. et al. A review of tissue inhibitor of metalloproteinases-3 (TIMP-3) and experimental analysis of its effect on primary tumor growth. Biochem Cell Biol. 1996; 74(6):853–62.
26. Gomez DE, Alonso DF, Yoshiji H, Thorgeirsson UP. Tissue inhibitors of metalloproteinases: structure, regulation and biological functions. Eur J Cell Biol. 1997; 74(2):111–22.
27. Qi JH, Ebrahem Q, Moore N, Murphy G, Claesson-Welsh L, Bond M. et al. A novel function for tissue inhibitor of metalloproteinases-3 (TIMP3): inhibition of angiogenesis by blockage of VEGF binding to VEGF receptor-2. Nat Med. 2003; 9(4):407–15.
28. Guan Z, Zhang J, Song S, Dai D. Promoter methylation and expression of TIMP3 gene in gastric cancer. Diagn Pathol. 2013; 8:110.
crossref
29. Catasus L, Pons C, Munoz J, Espinosa I, Prat J. Promoter hypermethylation contributes to TIMP3 down-regulation in high stage endometrioid endometrial carcinomas. Histopathology. 2013; 62(4):632–41.
30. Sun W, Zaboli D, Wang H, Liu Y, Arnaoutakis D, Khan T. et al. Detection of TIMP3 promoter hypermethylation in salivary rinse as an independent predictor of local recurrence-free survival in head and neck cancer. Clin Cancer Res. 2012; 18(4):1082–91.
31. Brait M, Loyo M, Rosenbaum E, Ostrow KL, Markova A, Papagerakis S. et al. Correlation between BRAF mutation and promoter methylation of TIMP3, RARbeta2 and RASSF1A in thyroid cancer. Epigenetics. 2012; 7(7):710–9.
32. Miyauchi S, Gopal E, Fei YJ, Ganapathy V. Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids. J Biol Chem. 2004; 279(14):13293–6.
crossref
33. Li H, Myeroff L, Smiraglia D, Romero MF, Pretlow TP, Kasturi L. et al. SLC5A8, a sodium transporter, is a tumor suppressor gene silenced by methylation in human colon aberrant crypt foci and cancers. Proc Natl Acad Sci USA. 2003; 100(14):8412–7.
34. Elangovan S, Pathania R, Ramachandran S, Ananth S, Padia RN, Srinivas SR. et al. Molecular mechanism of SLC5A8 inactivation in breast cancer. Mol Cell Biol. 2013; 33(19):3920–35.
35. Park JY, Kim D, Yang M, Park HY, Lee SH, Rincon M. et al. Gene silencing of SLC5A8 identified by genome-wide methylation profiling in lung cancer. Lung Cancer. 2013; 79(3):198–204.
36. Park JY, Helm JF, Zheng W, Ly QP, Hodul PJ, Centeno BA. et al. Silencing of the candidate tumor suppressor gene solute carrier family 5 member 8 (SLC5A8) in human pancreatic cancer. Pancreas. 2008; 36(4):e32–9.
37. Zane M, Agostini M, Enzo MV, Casal Ide E, Del Bianco P, Torresan F. et al. Circulating cell-free DNA, SLC5A8 and SLC26A4 hypermethylation, BRAF(V600E): A non-invasive tool panel for early detection of thyroid cancer. Biomed Pharmacother. 2013; 67(8):723–30.
38. Lam AK, Lo CY, Leung P, Lang BH, Chan WF, Luk JM. Clinicopathological roles of alterations of tumor suppressor gene p16 in papillary thyroid carcinoma. Ann Surg Oncol. 2007; 14(5):1772–9.
crossref
39. Serrano J, Goebel SU, Peghini PL, Lubensky IA, Gibril F, Jensen RT. Alterations in the p16INK4a/CDKN2A tumor suppressor gene in gastrinomas. J Clin Endocrinol Metab. 2000; 85(11):4146–56.
crossref
40. Kim YJ, Kim HS, Ha YJ, Lee HY, Park KG, Kim MK. et al. p16(INK4A) promoter hypermethylation and expression of p16(INK4A), cyclin D1, and Rb in papillary thyroid carcinoma. Korean J Med. 2010; 78(3):333–40.
41. Schagdarsurengin U, Gimm O, Hoang-Vu C, Dralle H, Pfeifer GP, Dammann R. Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma. Cancer Res. 2002; 62(13):3698–701.
42. Soprano DR, Qin P, Soprano KJ. Retinoic acid receptors and cancers. Annu Rev Nutr. 2004; 24:201–21.
crossref
43. Hoque MO, Rosenbaum E, Westra WH, Xing M, Ladenson P, Zeiger MA. et al. Quantitative assessment of promoter methylation profiles in thyroid neoplasms. J Clin Endocrinol Metab. 2005; 90(7):4011–8.
44. Kiseljak-Vassiliades K, Xing M. Association of cigarette smoking with aberrant methylation of the tumor suppressor gene RARbeta2 in papillary thyroid cancer. Front Endocrinol (Lausanne). 2011; 2:99.
crossref
45. Schneider-Stock R, Roessner A, Ullrich O. DAP-kinase–protector or enemy in apoptotic cell death. Int J Biochem Cell Biol. 2005; 37(9):1763–7.
crossref
46. Nomura T, Tahara T, Shiroeda H, Minato T, Matsue Y, Hayashi R. et al. Influence of HRH2 promoter polymorphism on aberrant DNA methylation of DAPK and CDH1 in the gastric epithelium. BMC Gastroenterol. 2013; 13:1.
crossref
47. Eisenberg-Lerner A, Kimchi A. DAPk silencing by DNA methylation conveys resistance to anti EGFR drugs in lung cancer cells. Cell Cycle. 2012; 11(11):2051.
crossref
48. Xiaofang L, Kun T, Shaoping Y, Zaiqiu W, Hailong S. Correlation between promoter methylation of p14(ARF), TMS1/ASC, and DAPK, and p53 mutation with prognosis in cholangiocarcinoma. World J Surg Oncol. 2012; 10:5.
crossref
49. Coffman JA. Runx transcription factors and the developmental balance between cell proliferation and differentiation. Cell Biol Int. 2003; 27(4):315–24.
crossref
50. Blyth K, Cameron ER, Neil JC. The RUNX genes: gain or loss of function in cancer. Nat Rev Cancer. 2005; 5(5):376–87.
crossref
51. De Falco V, Castellone MD, De Vita G, Cirafici AM, Hershman JM, Guerrero C. et al. RET/papillary thyroid carcinoma oncogenic signaling through the Rap1 small GTPase. Cancer Res. 2007; 67(1):381–90.
52. Wang Z, Dillon TJ, Pokala V, Mishra S, Labudda K, Hunter B. et al. Rap1-mediated activation of extracellular signal-regulated kinases by cyclic AMP is dependent on the mode of Rap1 activation. Mol Cell Biol. 2006; 26(6):2130–45.
53. Zhang L, Chenwei L, Mahmood R, van Golen K, Greenson J, Li G. et al. Identification of a putative tumor suppressor gene Rap1GAP in pancreatic cancer. Cancer Res. 2006; 66(2):898–906.
54. Tsygankova OM, Prendergast GV, Puttaswamy K, Wang Y, Feldman MD, Wang H. et al. Downregulation of Rap1GAP contributes to Ras transformation. Mol Cell Biol. 2007; 27(19):6647–58.
55. Zuo H, Gandhi M, Edreira MM, Hochbaum D, Nimgaonkar VL, Zhang P. et al. Downregulation of Rap1GAP through epigenetic silencing and loss of heterozygosity promotes invasion and progression of thyroid tumors. Cancer Res. 2010; 70(4):1389–97.
56. Kondo T, Ezzat S, Asa SL. Pathogenetic mechanisms in thyroid follicular-cell neoplasia. Nat Rev Cancer. 2006; 6(4):292–306.
crossref
57. Xing M. BRAF mutation in thyroid cancer. Endocr Relat Cancer. 2005; 12(2):245–62.
crossref
58. Groussin L, Fagin JA. Significance of BRAF mutations in papillary thyroid carcinoma: prognostic and therapeutic implications. Nat Clin Pract Endocrinol Metab. 2006; 2(4):180–1.
crossref
59. Lupi C, Giannini R, Ugolini C, Proietti A, Berti P, Minuto M. et al. Association of BRAF V600E mutation with poor clinicopathological outcomes in 500 consecutive cases of papillary thyroid carcinoma. J Clin Endocrinol Metab. 2007; 92(11):4085–90.
60. Xing M, Westra WH, Tufano RP, Cohen Y, Rosenbaum E, Rhoden KJ. et al. BRAF mutation predicts a poorer clinical prognosis for papillary thyroid cancer. J Clin Endocrinol Metab. 2005; 90(12):6373–9.
61. Li X, Abdel-Mageed AB, Kandil E. BRAF mutation in papillary thyroid carcinoma. Int J Clin Exp Med. 2012; 5(4):310–5.
62. Kim TH, Park YJ, Lim JA, Ahn HY, Lee EK, Lee YJ. et al. The association of the BRAF(V600E) mutation with prognostic factors and poor clinical outcome in papillary thyroid cancer: a meta-analysis. Cancer. 2012; 118(7):1764–73.
63. Santoro A, Pannone G, Carosi MA, Francesconi A, Pescarmona E, Russo GM. et al. BRAF mutation and RASSF1A expression in thyroid carcinoma of southern Italy. J Cell Biochem. 2013; 114(5):1174–82.
64. Xing M, Cohen Y, Mambo E, Tallini G, Udelsman R, Ladenson PW. et al. Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res. 2004; 64(5):1664–8.
65. de Vogel S, Weijenberg MP, Herman JG, Wouters KA, de Goeij AF, van den Brandt PA. et al. MGMT and MLH1 promoter methylation versus APC, KRAS and BRAF gene mutations in colorectal cancer: indications for distinct pathways and sequence of events. Ann Oncol. 2009; 20(7):1216–22.
66. Guan H, Ji M, Hou P, Liu Z, Wang C, Shan Z. et al. Hypermethylation of the DNA mismatch repair gene hMLH1 and its association with lymph node metastasis and T1799A BRAF mutation in patients with papillary thyroid cancer. Cancer. 2008; 113(2):247–55.
67. Santos JC, Bastos AU, Cerutti JM, Ribeiro ML. Correlation of MLH1 and MGMT expression and promoter methylation with genomic instability in patients with thyroid carcinoma. BMC Cancer. 2013; 13:79.
crossref
68. Jo YS, Li S, Song JH, Kwon KH, Lee JC, Rha SY. et al. Influence of the BRAF V600E mutation on expression of vascular endothelial growth factor in papillary thyroid cancer. J Clin Endocrinol Metab. 2006; 91(9):3667–70.
69. Fresno Vara JA, Casado E, de Castro J, Cejas P, Belda-Iniesta C, Gonzalez-Baron M. PI3K/Akt signalling pathway and cancer. Cancer Treat Rev. 2004; 30(2):193–204.
70. Alvarez-Nunez F, Bussaglia E, Mauricio D, Ybarra J, Vilar M, Lerma E. et al. PTEN promoter methylation in sporadic thyroid carcinomas. Thyroid. 2006; 16(1):17–23.
71. Hou P, Ji M, Xing M. Association of PTEN gene methylation with genetic alterations in the phosphatidylinositol 3-kinase/AKT signaling pathway in thyroid tumors. Cancer. 2008; 113(9):2440–7.
72. Donninger H, Vos MD, Clark GJ. The RASSF1A tumor suppressor. J Cell Sci. 2007; 120(Pt 18):3163–72.
crossref
73. Agathanggelou A, Cooper WN, Latif F. Role of the Ras-association domain family 1 tumor suppressor gene in human cancers. Cancer Res. 2005; 65(9):3497–508.
crossref
74. Nilsson M. Iodide handling by the thyroid epithelial cell. Exp Clin Endocrinol Diabetes. 2001; 109(1):13–7.
crossref
75. Caillou B, Troalen F, Baudin E, Talbot M, Filetti S, Schlumberger M. et al. Na+/I- symporter distribution in human thyroid tissues: an immunohistochemical study. J Clin Endocrinol Metab. 1998; 83(11):4102–6.
76. Sherman SI. Thyroid carcinoma. Lancet. 2003; 361(9356):501–11.
77. Smith JA, Fan CY, Zou C, Bodenner D, Kokoska MS. Methylation status of genes in papillary thyroid carcinoma. Arch Otolaryngol Head Neck Surg. 2007; 133(10):1006–11.
crossref
78. Galrao AL, Sodre AK, Camargo RY, Friguglietti CU, Kulcsar MA, Lima EU. et al. Methylation levels of sodium-iodide symporter (NIS) promoter in benign and malignant thyroid tumors with reduced NIS expression. Endocrine. 2013; 43(1):225–9.
79. Stephen JK, Chitale D, Narra V, Chen KM, Sawhney R, Worsham MJ. DNA methylation in thyroid tumorigenesis. Cancers (Basel). 2011; 3(2):1732–43.
crossref
80. Kopp P. The TSH receptor and its role in thyroid disease. Cell Mol Life Sci. 2001; 58(9):1301–22.
81. Xing M, Usadel H, Cohen Y, Tokumaru Y, Guo Z, Westra WB. et al. Methylation of the thyroid-stimulating hormone receptor gene in epithelial thyroid tumors: a marker of malignancy and a cause of gene silencing. Cancer Res. 2003; 63(9):2316–21.
82. Everett LA, Glaser B, Beck JC, Idol JR, Buchs A, Heyman M. et al. Pendred syndrome is caused by mutations in a putative sulphate transporter gene (PDS). Nat Genet. 1997; 17(4):411–22.
83. Xing M, Tokumaru Y, Wu G, Westra WB, Ladenson PW, Sidransky D. Hypermethylation of the Pendred syndrome gene SLC26A4 is an early event in thyroid tumorigenesis. Cancer Res. 2003; 63(9):2312–5.
84. Xu XC, el-Naggar AK, Lotan R. Differential expression of galectin-1 and galectin-3 in thyroid tumors. Potential diagnostic implications. Am J Pathol. 1995; 147(3):815–22.
85. Keller S, Angrisano T, Florio E, Pero R, Decaussin-Petrucci M, Troncone G. et al. DNA methylation state of the galectin-3 gene represents a potential new marker of thyroid malignancy. Oncol Lett. 2013; 6(1):86–90.
86. Sassa M, Hayashi Y, Watanabe R, Kikumori T, Imai T, Kurebayashi J. et al. Aberrant promoter methylation in overexpression of CITED1 in papillary thyroid cancer. Thyroid. 2011; 21(5):511–7.

Fig. 1.
CpG island methylation. (A) In a normal cell, CpG islands have no methylated cytosine residue and allow transcriptional activity. (B) DNA methylation at the 5 position of cytosine has the specific effect of reducing gene expression by gene silencing. Methylated CpG islands contribute to loss of gene function.
jkta-7-118f1.tif
Fig. 2.
Thyroidal iodide-metabolizing molecules. A unique physiological function of thyroid gland is ability to uptake, concentrate and use iodide to synthesize thyroid hormones. This process involves several key protein molecules that are specifically expressed in follicular epithelial cells of the thyroid gland. Thyroid stimulating hormone receptor (TSHR) bound to TSH stimulates iodide transport into the thyroid gland by the sodium iodide symporter (NIS). The function of pendrin is to transport iodide into the follicular lumen from the thyroid cell. The genes of thyroid specific molecules (red arrow) are methylated in the promoter areas in thyroid tumors.
jkta-7-118f2.tif
Table 1.
Methylation of tumor suppressor genes associate with papillary thyroid cancer
Gene Methods nMe/N (%) Clinical signification References
TIMP3 QMSP 122/231 (53%) Extrathyroidal invasion Lymph node metastasis Multifocality Hu et al. 2006
QMSP 22/44 (51%) Lack of tissue inhibitor of metalloproteinase and antagonist of angiogenesis Bralt et al. 2012
SLC5A8 MSP 9/10 (90%) Thyroid tumorigenesis Porra et al. 2005
QMSP 76/231 (33%) Extrathyroidal invasion Multifocality Advanced tumor stage Hu et al. 2006
QMSP 34/86 (40%) Increase of the amount of circulating cf-DNA Zane et al. 2013
P16 MSP 17/35 (48%) No association with clinical characteristics Klm et al. 2010
MSP 18/44 (41%) High AMES risk group Advanced tumor stage Lam et al. 2007
MSP 10/25 (40%) No association with clinical characteristics Mohammadl-asl et al. 2011
MSP 3/12 (25%) Advanced tumor stage Schagdarsurengln et al. 2002
MSP 20/74 (27%) Metastasis High AMES risk group Wang et al. 2013
RAR β 2 QMSP 50/231 (22%) No association with clinical characteristics Hu et al. 2006
QMSP 23/138 (17%) Association with smoking Kiseljak-Vassiliades et al. 2011
DAPK QMSP 78/231 (34%) Multifocality Hu et al. 2006
RUNX3 QMSP 10/12 (83%) Diagnostic marker Ko et al. 2012
Rap1GAP MSP 58/75 (71%) Silencing of gene Zuo et al. 2010

AMES: age–metastasis–extent-size, cf–DNA: cell–free DNA, DAPK: death–associated protein kinase, MSP: methylation specific polymerase chain reaction, nMe/N: number of cases with methylation/total, QMSP: quantitative methylation specific polymerase chain reaction, Rap1GAP: Rap1 GTPase–activating protein, RAR β 2: retinoic acid receptor beta 2, RUNX3: Runt–related transcription factor 3, SLC5A8: solute carrier family 5 member 8, TIMP3: tissue inhibitor of metalloproteinase 3

Table 2.
Methylation of tumor suppressor genes associated with follicular thyroid carcinoma
Gene Methods Frequency (nMe/N [%])
 References
FA FTC PTC
PTEN MSP 5/6 (83%) 6/7 (86%) 21/46 (46%) Alvarez-Nuñez et al. 2006
QMSP 5/43 (12%) 25/65 (51%) No exam. Hou et al. 2008
PTC FTC Normal
RASSF1A QMSP 8/13 (62%) 7/10 (70%) 1/4 (25%) Schagdarsurengin et al. 2002
QMSP 6/30 (20%) 9/12 (75%) 0/14 (0%) Xing et al. 2004

FA: follicular adenoma, FTC: follicular thyroid cancer, MSP: methylation specific polymerase chain reaction, nMe/N: number of cases with methylation/total, PTC: papillary thyroid cancer, PTEN: phosphatase and tensin homolog gene, QMSP: quantitative methylation specific polymerase chain reaction, RASSF1A: ras association domain family 1 isoform A

TOOLS
Similar articles