Methylation of tumour suppressor genes associated with thyroid cancer.


Journal

Cancer biomarkers : section A of Disease markers
ISSN: 1875-8592
Titre abrégé: Cancer Biomark
Pays: Netherlands
ID NLM: 101256509

Informations de publication

Date de publication:
2019
Historique:
pubmed: 23 4 2019
medline: 23 11 2019
entrez: 23 4 2019
Statut: ppublish

Résumé

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.

Sections du résumé

BACKGROUND 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 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 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 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 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.

Identifiants

pubmed: 31006665
pii: CBM182265
doi: 10.3233/CBM-182265
doi:

Substances chimiques

Adaptor Proteins, Signal Transducing 0
DNA-Binding Proteins 0
LIM Domain Proteins 0
PDLIM4 protein, human 0
Repressor Proteins 0
TP73 protein, human 0
Tumor Protein p73 0
WIF1 protein, human 0

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

53-65

Auteurs

Anca Botezatu (A)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Iulia V Iancu (IV)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Adriana Plesa (A)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Dana Manda (D)

'CI Parhon' National Institute of Endocrinology, Bucharest, Romania.

Oana Popa (O)

'CI Parhon' National Institute of Endocrinology, Bucharest, Romania.

Marinela Bostan (M)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Mirela Mihaila (M)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Adrian Albulescu (A)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.
National Institute for Chemical pharmaceutical Research and Development, Calea Vitan, Romania.

Alina Fudulu (A)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Susana V Vladoiu (SV)

'CI Parhon' National Institute of Endocrinology, Bucharest, Romania.

Irina Huica (I)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Ruxandra Dobrescu (R)

'CI Parhon' National Institute of Endocrinology, Bucharest, Romania.
'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.

Gabriela Anton (G)

'Stefan S. Nicolau' Institute of Virology, Bucharest, Romania.

Corin Badiu (C)

'CI Parhon' National Institute of Endocrinology, Bucharest, Romania.
'Carol Davila' University of Medicine and Pharmacy, Bucharest, Romania.

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Classifications MeSH