Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas

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Ashutosh Kumar Arya1, Sanjay Kumar Bhadada2, Priyanka Singh1

  • 1Department of Endocrinology, Postgraduate Institute of Medical Education & Research (PGIMER), Chandigarh, India.

Scientific Reports
|June 11, 2017
PubMed

Insights

Methylation inactivates tumor suppressor genes CDKN2A, CDKN2B, and RASSF1A in parathyroid adenomas, leading to CCND1 upregulation and potential tumor growth.

Area of Science:

  • Endocrinology
  • Molecular Biology
  • Oncology

Background:

  • Cyclin D1 (CCND1) is upregulated in parathyroid adenomas.
  • Cyclin-dependent kinase (CDK) inhibitors (CDKN2A, CDKN2B) and RASSF1A are tumor suppressors involved in cell cycle arrest.

Purpose of the Study:

  • Investigate methylation-mediated inactivation of CDKN2A, CDKN2B, and RASSF1A in parathyroid adenomas.
  • Correlate gene expression and methylation with clinicopathological features.

Main Methods:

  • Analyzed gene expression of CCND1, CDKN2A, CDKN2B, and RASSF1A in 30 parathyroid adenomas and normal tissue.
  • Assessed DNA promoter methylation of CCND1 regulators.

Main Results:

  • Significant gene expression reduction for CDKN2A (0.35-fold), CDKN2B (0.45-fold), and RASSF1A (0.39-fold) in adenomas vs. normal tissue.
  • Hypermethylation observed in 50% of CDKN2A, 47% of CDKN2B, and 90% of RASSF1A promoter regions.
  • Inverse relationship found between CDKN2A/CDKN2B expression and CCND1 expression.

Conclusions:

  • Promoter hypermethylation correlates with down-regulation of CCND1 regulatory genes in sporadic parathyroid adenomas.
  • This dysregulation of cell cycle mechanisms may contribute to parathyroid tumorigenesis.

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