Diagnostic Value of RASSF1A gene DNA methylation in Differential Diagnosis of Thyroid Benign Tumors and Papillary Thyroid Carcinoma

Document Type : Original Article

Authors

1 Department of Biochemistry, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran

2 Department of Veterinary medicine, School of Agriculture, Shoushtar Branch, Islamic Azad University, Shoushtar, Iran

Abstract

Thyroid cancer is the most common endocrine malignancy that its incidence has
continuously increased in recent decades all over the world. Thyroid cancer in Iran
is the seventh most common cancer in women and the 14th in men and the 11th most
common cancer in both genders. The study on the methylation status of RASSF1A
gene promoter has shown that this gene is methylated in 35% of benign and
malignant thyroid tumors. Hypermethylation of the RASSF1A gene use for the
differentiation of benign tumors from malignant of thyroid gland. The aim of this
study was to determine the sensitivity and specificity of DNA methylation of
RASSF1A gene in the differential diagnosis of benign tumors from papillary thyroid
carcinoma.160 samples of patients with malignant thyroid tumors (80 samples) and
benign thyroid (80 samples) were entered into this study from all patients referring
to Ahwaz medical centers. The Hypermethylation of the gene after DNA extraction
was done by COBRA method. Finally, for calculating sensitivity and specificity of
the two tests were done by epidemiological calculations.The sensitivity and
specificity of Hypermethylation of the RASSF1A gene test were 91.25% and 15%
respectively.Hypermethylation of the promoter of the RASSF1A gene as a diagnosis
test is more sensitive to differential diagnosis of benign tumors from papillary
thyroid carcinoma.

Keywords


Burbee, D.G., E. Forgacs, S. Zochbauer-Muller, L. Shivakumar, K. Fong, B. Gao, et al., Epigenetic inactivation of RASSF1A in lung and breast cancers and malignant phenotype suppression. J Natl Cancer Inst, 2001. 93, 691-9.
Dammann, R., C. Li, J.H. Yoon, P.L. Chin, S. Bates, and G.P. Pfeifer, Epigenetic inactivation of a RAS association domain family protein from the lung tumour suppressor locus 3p21.3. Nat Genet, 2000. 25, 315-9.
Dreijerink, K., E. Braga, I. Kuzmin, L. Geil, F.M. Duh, D. Angeloni, et al., The candidate tumor suppressor gene, RASSF1A, from human chromosome 3p21.3 is involved in kidney tumorigenesis. Proc Natl Acad Sci U S A, 2001. 98, 7504-9.
Howlader N, Noone AM, Krapcho M, Neyman N, Aminou R, Waldron W, et al, editors. SEER Cancer Statistics Review, 1975- 2009 (Vintage 2009 Populations), National  Cancer Institute [Internet]. 2012 Apr [cited 2018 Jan 15]. Available from:          https://seer.cancer.gov/archive/csr/1975_2009_pops09/
Hu, S., D. Liu, R.P. Tufano, K.A. Carson, E. Rosenbaum, Y. Cohen, 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, 2322-9.
Kebebew, E., M. Peng, E. Reiff, Q.Y. Duh, O.H. Clark, and A. McMillan, Diagnostic and prognostic value of angiogenesis-modulating genes in malign thyroid neoplasms. Surgery, 2005. 138, 1102-9; discussion 1109-10.
Lee, J.H., E.S. Lee, and Y.S. Kim, Clinicopathologic significance of BRAF V600E mutation in papillary carcinomas of the thyroid: a meta-analysis. Cancer, 2007. 110, 38-46.
Nakamura, N., J.A. Carney, L. Jin, S. Kajita, J. Pallares, H. Zhang, et al., RASSF1A and NORE1A methylation and BRAFV600E mutations in thyroid tumors. Lab Invest, 2005. 85, 1065-75.
Pfeifer, G.P. and R. Dammann, Methylation of the tumor suppressor gene RASSF1A in human tumors. Biochemistry (Mosc), 2005. 70, 576-83.
Ruebel, K.H., L. Jin, X. Qian, B.W. Scheithauer, K. Kovacs, N. Nakamura, et al., Effects of DNA methylation on galectin-3 expression in pituitary tumors. Cancer Res, 2005. 65, 1136-40.
Shivakumar, L., J. Minna, T. Sakamaki, R. Pestell, and M.A. White, The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation. Mol Cell Biol, 2002. 22: pp. 4309-18.
Soares, P., V. Maximo, and M. Sobrinho-Simoes, Molecular pathology of papillary, follicular and Hurthle cell carcinomas of the thyroid. Arkh Patol, 2003. 65, 45-7.
Segev, D.L., C. Umbricht, and M.A. Zeiger, Molecular pathogenesis of thyroid cancer. Surg Oncol, 2003. 12, 69-90.
Schagdarsurengin, U., O. Gimm, C. Hoang-Vu, H. Dralle, G.P. Pfeifer, and R. Dammann, Frequent epigenetic silencing of the CpG island promoter of RASSF1A in thyroid carcinoma. Cancer Res, 2002. 62, 3698-701.
Shivakumar, L., J. Minna, T. Sakamaki, R. Pestell, and M.A. White, The RASSF1A tumor suppressor blocks cell cycle progression and inhibits cyclin D1 accumulation. Mol Cell Biol, 2002. 22, 4309-18
Sakashita, K., K. Mimori, F. Tanaka, Y. Kamohara, H. Inoue, T. Sawada, et al., Clinical significance of loss of Fhl1 expression in human gastric cancer. Ann Surg Oncol, 2008. 15, 2293-300.
Tuttle RM, Ball DW, Byrd D, Dilawari RA, Doherty GM, Duh QY, et al; NationalComprehensive Cancer Network. Thyroid carcinoma. J Natl Compr Canc Netw   2010;8(11), 1228-74.
Taghavi Kojidi H, Farzadfar F, Peykari N, Larijani B, Rahimzadeh S, Rezaei-Darzi E, et al. A comprehensive study on national and sub national trend in thyroid cancer prevalence  in the Iranian population, 1990-2010. Iran J Diabetes Metab 2016;15(2), 91-100
Trovisco, V., P. Soares, and M. Sobrinho-Simoes, B-RAF mutations in the etiopathogenesis, diagnosis, and prognosis of thyroid carcinomas. Hum Pathol, 2006. 37, 781-6.
Xiong, Z. and P.W. Laird, COBRA: a sensitive and quantitative DNA methylation assay. Nucleic Acids Res, 1997. 25, 2532-4.
Xing, M., Y. Cohen, E. Mambo, G. Tallini, R. Udelsman, P.W. Ladenson, et al., Early occurrence of RASSF1A hypermethylation and its mutual exclusion with BRAF mutation in thyroid tumorigenesis. Cancer Res, 2004. 64, 1664-8.
Volume 1, Issue 2
April 2019
Pages 17-23
  • Receive Date: 03 June 2019
  • Revise Date: 02 October 2019
  • Accept Date: 15 December 2019
  • First Publish Date: 15 December 2019