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5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma

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Title: 5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma
Author(s): Barazeghi, E
Gill, AJ
Sidhu, S
Norlen, O
Dina, R
Palazzo, FF
Hellman, P
Stalberg, P
Westin, G
Item Type: Journal Article
Abstract: Background Primary hyperparathyroidism is characterized by enlarged parathyroid glands due to an adenoma (80–85 %) or multiglandular disease (~15 %) causing hypersecretion of parathyroid hormone (PTH) and generally hypercalcemia. Parathyroid cancer is rare (<1–5 %). The epigenetic mark 5-hydroxymethylcytosine (5hmC) is reduced in various cancers, and this may involve reduced expression of the ten-eleven translocation 1 (TET1) enzyme. Here, we have performed novel experiments to determine the 5hmC level and TET1 protein expression in 43 parathyroid adenomas (PAs) and 17 parathyroid carcinomas (PCs) from patients who had local invasion or metastases and to address a potential growth regulatory role of TET1. Results The global 5hmC level was determined by a semi-quantitative DNA immune-dot blot assay in a smaller number of tumors. The global 5hmC level was reduced in nine PCs and 15 PAs compared to four normal tissue samples (p < 0.05), and it was most severely reduced in the PCs. By immunohistochemistry, all 17 PCs stained negatively for 5hmC and TET1 showed negative or variably heterogeneous staining for the majority. All 43 PAs displayed positive 5hmC staining, and a similar aberrant staining pattern of 5hmC and TET1 was seen in about half of the PAs. Western blotting analysis of two PCs and nine PAs showed variable TET1 protein expression levels. A significantly higher tumor weight was associated to PAs displaying a more severe aberrant staining pattern of 5hmC and TET1. Overexpression of TET1 in a colony forming assay inhibited parathyroid tumor cell growth. Conclusions 5hmC can discriminate between PAs and PCs. Whether 5hmC represents a novel marker for malignancy warrants further analysis in additional parathyroid tumor cohorts. The results support a growth regulatory role of TET1 in parathyroid tissue.
Publication Date: 12-Mar-2016
Date of Acceptance: 2-Mar-2016
URI: http://hdl.handle.net/10044/1/39808
DOI: http://dx.doi.org/10.1186/s13148-016-0197-2
ISSN: 1868-7083
Publisher: BioMed Central
Journal / Book Title: Clinical Epigenetics
Volume: 8
Copyright Statement: This article is distributed under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.
Keywords: Science & Technology
Life Sciences & Biomedicine
Oncology
5-hydroxymethylcytosine
5hmC
Parathyroid cancer
Primary hyperparathyroidism
TET1
TET PROTEINS
CANCER GROWTH
WNT PATHWAY
DNA
5-METHYLCYTOSINE
PARAFIBROMIN
EXPRESSION
INHIBITORS
MUTATIONS
CATENIN
5-hydroxymethylcytosine
5hmC
Parathyroid cancer
Primary hyperparathyroidism
TET1
Adenoma
Adolescent
Adult
Aged
Blotting, Western
Case-Control Studies
Cytosine
DNA-Binding Proteins
Humans
Middle Aged
Parathyroid Glands
Parathyroid Neoplasms
Proto-Oncogene Proteins
Real-Time Polymerase Chain Reaction
Young Adult
Parathyroid Glands
Humans
Adenoma
Parathyroid Neoplasms
Cytosine
DNA-Binding Proteins
Proto-Oncogene Proteins
Blotting, Western
Case-Control Studies
Adolescent
Adult
Aged
Middle Aged
Young Adult
Real-Time Polymerase Chain Reaction
Publication Status: Published
Article Number: 31
Appears in Collections:Department of Medicine
Faculty of Medicine



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