International journal of thyroidology

Korean Thyroid Association (대한갑상선학회)
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Relation between RASSF1A Methylation and BRAF Mutation in Thyroid Tumor

갑상선 종양에서 RASSF1A 메틸화와 BRAF 유전자 변이에 관한 연구

  • Oh, Kyoung Ho (Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine) ;
  • Jung, Kwang Yoon (Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine) ;
  • Baek, Seung Kuk (Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine) ;
  • Woo, Jeong Soo (Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine) ;
  • Cho, Jae Gu (Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine) ;
  • Kwon, Soon Young (Department of Otorhinolaryngology-Head and Neck Surgery, Korea University College of Medicine)
  • 오경호 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 정광윤 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 백승국 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 우정수 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 조재구 (고려대학교 의과대학 이비인후-두경부외과학교실) ;
  • 권순영 (고려대학교 의과대학 이비인후-두경부외과학교실)
  • Received : 2018.10.23
  • Accepted : 2018.11.12
  • Published : 2018.11.30
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Abstract

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

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