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5-Hydroxymethylcytosine discriminates between parathyroid adenoma and carcinoma
#MMPMID26973719
Barazeghi E
; Gill AJ
; Sidhu S
; Norlén O
; Dina R
; Palazzo FF
; Hellman P
; Stålberg P
; Westin G
Clin Epigenetics
2016[]; 8
(?): 31
PMID26973719
show ga
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.