Loss of 5-Hydroxymethylcytosine is an Epigenetic Hallmark of Thyroid Carcinomas with TERT Promoter Mutations

AbstractEpigenetic dysregulation is a hallmark of cancer, and aberrant methylation of cytosine residues plays a crucial role in abnormal gene expression in cancer cells. Recent studies demonstrate that 5-hydroxymethylcytosine (5-hmC) generated through 5-methylcytosine (5-mC) oxidation is significantly depleted in various cancers. However, whether 5-hmC levels change during the stepwise progression of thyroid carcinoma and the mechanisms underlying this effect remain unknown. The aims of this study were (i) to assess 5-hmC levels in normal and cancerous thyroid tissues, and (ii) identify clinicopathologic and genetic factors associated with the dysregulated hydroxymethylation of cytosine. Enzyme-linked immunosorbent assay (ELISA) showed that 5-hmC was significantly reduced inTERT promoter-mutated papillary thyroid carcinomas (PTCs) and anaplastic thyroid carcinomas (ATCs), while there was no significant difference in 5-hmC levels betweenTERT promoter-wild-type PTCs and normal thyroid tissues. Results of semi-quantitative analysis of 5-hmC through immunohistochemistry correlated well with those of ELISA and confirmed the loss of 5-hmC in tumor cells. Immunohistochemistry confirmed lower 5-hmC positivity inTERT promoter-mutated PTCs (n = 10) and ATCs (n = 4) than in normal thyroid tissues (n  =  8) andTERT promoter-wild-type PTCs (n = 63). Tumor size (>  1 cm) and advanced stage were associated with decreased global 5-hmC in PTCs, while age, gross extrathyroidal inv...
Source: Endocrine Pathology - Category: Pathology Source Type: research