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Relation between RASSF1A Methylation and BRAF Mutation in Thyroid Tumor
Int J Thyroidol 2018;11(2):123-129
Published online November 30, 2018;
© 2018 Korean Thyroid Association.

Kyoung Ho Oh, Kwang Yoon Jung, Seung Kuk Baek, Jeong Soo Woo, Jae Gu Cho and Soon Young Kwon

Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine, Seoul, Korea
Correspondence to: Soon Young Kwon, MD, PhD, Department of Otorhinolaryngology-Head and Neck Surgery, Korea University Ansan Hospital, 123 Jeokgeum-ro, Danwon-gu, Ansan 15355, Korea
Tel: 82-31-412-5170, Fax: 82-31-412-5174, E-mail:
Received October 23, 2018; Revised November 12, 2018; Accepted November 12, 2018.
This is an open-access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (, which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.
Background and Objectives: Hypermethylation of the tumor suppressor gene RASSF1A and activating mutation of BRAF gene have been recently reported in thyroid cancers. To investigate the role of these two epigenetic and genetic alterations in thyroid tumor progression, methylation of RASSF1A and BRAF mutation were examined in thyroid tumors. Materials and Methods: During 2007 to 2017, 69 papillary carcinomas, 18 nodular hyperplasia, 3 follicular carcinomas, and 13 follicular adenomas were selected. The methylation-specific polymerase chain reaction (MSP) technique was used in detecting RASSF1A methylation and polymerase chain reaction (PCR)-single-stranded conformation polymorphism and sequencing were used for BRAF gene mutation study. Results: The hypermethylation of the RASSF1A gene was found in 84.6%, 100% and 57.9% of follicular adenomas, follicular carcinomas, and papillary carcinomas, respectively. Nodular hyperplasia showed a hypermethylation in 33.3%. The BRAF mutation at V600E was found in 60.7% of papillary carcinoma and 27.0% of nodular hyperplasia, but none of follicular neoplasms. The BRAF mutation was correlated with the lymph node metastasis and MACIS clinical stage. There is an inverse correlation between RASSF1A methylation and BRAF mutation in thyroid lesions. Conclusion: Epigenetic inactivation of RASSF1A through aberrant methylation is considered to be an early step in thyroid tumorigenesis, and the BRAF mutation plays an important role in the carcinogenesis of papillary carcinoma, providing a genetic marker.
Keywords : RASSF1A, Methylation, BRAF, Mutation, Thyroid

November 2018, 11 (2)