'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.
'CI Parhon' National Institute of Endocrinology, Bucharest, Romania.
Cancer Biomark. 2019;25(1):53-65. doi: 10.3233/CBM-182265.
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.
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.
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.
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.
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.
甲状腺癌是全球最常见的内分泌恶性肿瘤。DNA 甲基化的改变可导致正常活跃基因沉默，尤其是肿瘤抑制基因（TSG）或正常沉默基因的激活。
本研究旨在评估甲状腺肿瘤标志物的启动子甲基化程度，并确定其与甲状腺癌发生的关系。
为了生成甲状腺肿瘤中涉及的 TSG 的综合 DNA 甲基化特征，我们使用 Human TSG EpiTect Methyl II Signature PCR Array-Qiagen 对 24 个样本（滤泡性腺瘤和甲状腺乳头状癌）与正常甲状腺组织进行比较。我们使用 qMS-PCR 扩展了对三个 TSG（TP73、WIF1、PDLIM4）的评估。使用 GraphPad Prism 进行统计分析。
我们注意到四个重要的基因 NEUROG1、ESR1、RUNX3、MLH1，其启动子在肿瘤样本中与正常样本相比发生了甲基化。我们发现了甲状腺肿瘤的新特征：TP73、WIF1 和 PDLIM4 TSG 的甲基化，这可能有助于甲状腺肿瘤的发生。BRAF V600E 突变和 RET/PTC 重排与 TIMP3 和 CDH13、RARB 甲基化之间分别存在显著相关性。
TSG 启动子的高甲基化是癌症的一个标志，使用甲基化定量方法的检测适合甲状腺癌的诊断和预后。
