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Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their BRAF V600E mutation status

  • Endocrine Genetics/Epigenetics
  • Published:
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Abstract

Promoter hypermethylation of multiple genes have been identified to play a role in thyroid cancers and most prominent among them is TSHR gene promoter hypermethylation in particular showing a close association with BRAF gene-altered status. Thus, the aim of this study was to analyze the TSHR gene promoter hypermethylation in a series of thyroid tumor tissues in the backdrop of their BRAF gene mutational status. Methylation-specific PCR (MS-PCR) was used for detection of promoter methylation while BRAF gene mutational status was analyzed by PCR followed by DNA sequencing in the same series of 60 thyroid tumor tissues. The promoter region of TSHR gene was found to be methylated in 25 % (15 of 60) of the thyroid cancer patients. Patients having elevated TSH levels showed strong association with methylation (OR = 4.0, P = 0.02). BRAF V600E mutation was found in 25 % (15 of 60) patients and among them TSHR promoter was methylated in 73.3 % (11 of 15) patients and only 26.7 % (4 of 15) patients with mutated BRAF showed the absence of TSHR promoter methylation. We found a significant association between the presence of methylation in TSHR with the BRAF V600E mutation-positive cases (P < 0.05). In conclusion, our study showed a high implication of TSHR gene methylation and its significant association with BRAF V600E mutation in thyroid tumors, depicting a positive connection between TSHR pathway and MAP Kinase pathway.

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Acknowledgments

The authors acknowledge the technical staff of operation theater of the Department of General Surgery. Their thanks are also due to the faculty members and research scholars of the Department of Clinical Biochemistry, SKIMS, Srinagar, Kashmir. This study was funded by Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, Kashmir, India-190011.

Conflict of interest

The authors declare that there is no conflict of interest that could be perceived as prejudicing the impartiality of the research reported.

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Authors and Affiliations

  1. Department of Clinical Biochemistry, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, Kashmir, India

    Mosin S. Khan & Syed Mudassar

  2. Advanced Centre for Human Genetics, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, Kashmir, India

    Arshad A. Pandith

  3. Department of Endocrinology, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, Kashmir, India

    Shariq R. Masoodi

  4. Department of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltmore, MD, 21201, USA

    Shariq R. Masoodi

  5. Department of General and Minimal Accesive Surgery, Sher-I-Kashmir Institute of Medical Sciences, Soura, Srinagar, 190011, Kashmir, India

    Khursheed A. Wani

  6. Department of Biotechnology, University of Kashmir, Srinagar, 190006, Kashmir, India

    Mahboob Ul Hussain

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  1. Mosin S. Khan
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  2. Arshad A. Pandith
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  3. Shariq R. Masoodi
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  4. Khursheed A. Wani
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  5. Mahboob Ul Hussain
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  6. Syed Mudassar
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Correspondence to Syed Mudassar.

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Khan, M.S., Pandith, A.A., Masoodi, S.R. et al. Epigenetic silencing of TSHR gene in thyroid cancer patients in relation to their BRAF V600E mutation status. Endocrine 47, 449–455 (2014). https://doi.org/10.1007/s12020-014-0319-6

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  • DOI: https://doi.org/10.1007/s12020-014-0319-6

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