• Methylated CpG Sites of the RAP1GAP Gene in the Anaplastic Thyroid Carcinoma
  • Bita Faam,1 Mehdi Totonchi,2 Reza M. Robati,3 Layasadat Khorsandi,4,*
    1. Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
    2. Department of Endocrinology and Female Infertility, Reproductive Biomedicine Research Center, Royan Institute for Reproductive Biomedicine, ACECR, Tehran, Iran.
    3. Skin Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.


  • Introduction: Anaplastic thyroid cancer (ATC) is a rare and extremely aggressive form of thyroid cancer that exhibits resistance to conventional treatment methods. Abnormal methylation may specify the molecular characteristics of ATC, thereby holding potential as biomarkers for early diagnosis. In this study, the gene and protein expression of RAP1GAP and methylation pattern of CpG74a, CpG74b, and CpG24 in an Iranian population with ATC was investigated.
  • Methods: Method: In this study, 40 individuals who underwent thyroidectomy during 2018 to 2020 were involved. Assessing the DNA methylation of selected CpGs were carried out using methylation-specific PCR method. The impact of a demethylating agent, specifically 5-Aza, was investigated within the thyroid cancer cell line (SW1736). The RAP1GAP gene and protein expression were examined.
  • Results: Accordingly, in ATC patients, the hypermethylation of CpG24 and CpG74a was significantly correlated with decreased level of RAP1GAP gene and protein expression. However; this correlation was not reported about CpG74b. The mRNA expression and protein level of RAP1GAP was considerably increased after de-methylation of SW1736 cells with 5-Aza as a demethylating agent.
  • Conclusion: This study identified RAP1GAP as a candidate tumor-suppressor gene in anaplastic thyroid carcinoma and hyper-methylation in the regulatory region of this gene may contribute to the ATC pathogenesis and this status can be a new potential prognostic biomarker.
  • Keywords: Anaplastic thyroid cancer, RAP1GAP, gene expression, Protein expression, DNA methylation