Methylation of tumour suppressor genes associated with thyroid cancer.

Abstract

Background: Thyroid carcinoma is the most common endocrine malignancy worldwide. Changes in DNA methylation can cause silencing of normally active genes, especially tumour suppressor genes (TSG) or activation of normally silent genes.

Objective: The aim of this study is to evaluate the degree of promoter methylation for a panel of markers for thyroid neoplasms and to establish their relationship with thyroid oncogenesis.

Methods: To generate a comprehensive DNA methylation signature of TSGs involved in thyroid neoplasia, we use Human TSG EpiTect Methyl II Signature PCR Array-Qiagen for 24 samples (follicular adenomas and papillary thyroid carcinomas) compared with normal thyroid tissue. We extended the evaluation for three TSGs (TP73, WIF1, PDLIM4) using qMS-PCR. Statistical analysis was performed with GraphPad Prism.

Results: We noted four important genes NEUROG1, ESR1, RUNX3, MLH1, which presented methylated promoter in tumour samples compared to normal. We found new characteristic of thyroid tumours: methylation of TP73, WIF1 and PDLIM4 TSGs, which can contribute to thyroid neoplasia. A significant correlation between BRAF V600E mutation and RET/PTC rearrangements with TIMP3 and CDH13, RARB methylation, respectively was observed.

Conclusions: TSGs promoter hypermethylation is a hallmark of cancer and a test that uses methylation quantification method is suitable for diagnosis and prognosis of thyroid cancer.