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

Abstract Cyclin D1, a G1-S phase regulator, is upregulated in parathyroid adenomas. Since cyclin-dependent kinase (CDK) inhibitors, CDKN2A and CDKN2B, and RASSF1A (Ras-association domain family 1, isoform A) are involved in G1-S phase arrest and act as potential tumor suppressor genes, we aimed to s...

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Autores principales:	Ashutosh Kumar Arya, Sanjay Kumar Bhadada, Priyanka Singh, Naresh Sachdeva, Uma Nahar Saikia, Divya Dahiya, Arunanshu Behera, Anil Bhansali, Sudhaker D. Rao
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/7a07776f1a83430da8cbd57ec4cd330f
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spelling	oai:doaj.org-article:7a07776f1a83430da8cbd57ec4cd330f2021-12-02T16:06:14ZPromoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas10.1038/s41598-017-03143-82045-2322https://doaj.org/article/7a07776f1a83430da8cbd57ec4cd330f2017-06-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-03143-8https://doaj.org/toc/2045-2322Abstract Cyclin D1, a G1-S phase regulator, is upregulated in parathyroid adenomas. Since cyclin-dependent kinase (CDK) inhibitors, CDKN2A and CDKN2B, and RASSF1A (Ras-association domain family 1, isoform A) are involved in G1-S phase arrest and act as potential tumor suppressor genes, we aimed to study potential methylation-mediated inactivation of these genes in parathyroid adenomas. Gene expressions of cyclin D1 (CCND1) and regulatory molecules (CDKN2A, CDKN2B and RASSF1A) was analysed in parathyroid adenoma tissues (n = 30). DNA promoter methylation of cyclin D1 regulators were assessed and correlated with clinicopathological features of the patients. Gene expression analysis showed a relative fold reductions of 0.35 for CDKN2A (p = 0.01), 0.45 for CDKN2B (P = 0.02), and 0.39 for RASSF1A (p < 0.01) in adenomatous compared to normal parathyroid tissue. There was an inverse relationship between the expressions of CDKN2A and CDKN2B with CCND1. In addition, the promoter regions of CDKN2A, CDKN2B, and of RASSF1A were significantly hyper-methylated in 50% (n = 15), 47% (n = 14), and 90% (n = 27) of adenomas respectively. In contrast, no such aberrant methylation of these genes was observed in normal parathyroid tissue. So, promoter hypermethylation is associated with down-regulation of CCND1 regulatory genes in sporadic parathyroid adenomas. This dysregulated cell cycle mechanism may contribute to parathyroid tumorigenesis.Ashutosh Kumar AryaSanjay Kumar BhadadaPriyanka SinghNaresh SachdevaUma Nahar SaikiaDivya DahiyaArunanshu BeheraAnil BhansaliSudhaker D. RaoNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-9 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Ashutosh Kumar Arya Sanjay Kumar Bhadada Priyanka Singh Naresh Sachdeva Uma Nahar Saikia Divya Dahiya Arunanshu Behera Anil Bhansali Sudhaker D. Rao Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
description	Abstract Cyclin D1, a G1-S phase regulator, is upregulated in parathyroid adenomas. Since cyclin-dependent kinase (CDK) inhibitors, CDKN2A and CDKN2B, and RASSF1A (Ras-association domain family 1, isoform A) are involved in G1-S phase arrest and act as potential tumor suppressor genes, we aimed to study potential methylation-mediated inactivation of these genes in parathyroid adenomas. Gene expressions of cyclin D1 (CCND1) and regulatory molecules (CDKN2A, CDKN2B and RASSF1A) was analysed in parathyroid adenoma tissues (n = 30). DNA promoter methylation of cyclin D1 regulators were assessed and correlated with clinicopathological features of the patients. Gene expression analysis showed a relative fold reductions of 0.35 for CDKN2A (p = 0.01), 0.45 for CDKN2B (P = 0.02), and 0.39 for RASSF1A (p < 0.01) in adenomatous compared to normal parathyroid tissue. There was an inverse relationship between the expressions of CDKN2A and CDKN2B with CCND1. In addition, the promoter regions of CDKN2A, CDKN2B, and of RASSF1A were significantly hyper-methylated in 50% (n = 15), 47% (n = 14), and 90% (n = 27) of adenomas respectively. In contrast, no such aberrant methylation of these genes was observed in normal parathyroid tissue. So, promoter hypermethylation is associated with down-regulation of CCND1 regulatory genes in sporadic parathyroid adenomas. This dysregulated cell cycle mechanism may contribute to parathyroid tumorigenesis.
format	article
author	Ashutosh Kumar Arya Sanjay Kumar Bhadada Priyanka Singh Naresh Sachdeva Uma Nahar Saikia Divya Dahiya Arunanshu Behera Anil Bhansali Sudhaker D. Rao
author_facet	Ashutosh Kumar Arya Sanjay Kumar Bhadada Priyanka Singh Naresh Sachdeva Uma Nahar Saikia Divya Dahiya Arunanshu Behera Anil Bhansali Sudhaker D. Rao
author_sort	Ashutosh Kumar Arya
title	Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
title_short	Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
title_full	Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
title_fullStr	Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
title_full_unstemmed	Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas
title_sort	promoter hypermethylation inactivates cdkn2a, cdkn2b and rassf1a genes in sporadic parathyroid adenomas
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/7a07776f1a83430da8cbd57ec4cd330f
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Promoter hypermethylation inactivates CDKN2A, CDKN2B and RASSF1A genes in sporadic parathyroid adenomas

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