Epigenetic alterations in human parathyroid tumors

Abstract

Epigenetics alterations are involved in tumorigenesis and have been identified in endocrine neoplasia. In particular, DNA methylation, microRNAs deregulations and histone methylation impairment are detected in tumors of the parathyroid glands. Parathyroid tumors are the second most common endocrine neoplasia following thyroid cancer in women, and it is associated with primary hyperparathyroidism, a disease sustained by PTH hypersecretion. Despite the hallmark of global promoter hypomethylations was not detectable in parathyroid tumors, increase of hypermethylation in specific CpG islands was detected in the progression from benign to malignant parathyroid tumors. Furthermore, deregulation of a panel of embryonic-related microRNAs (miRNAs) was documented in parathyroid tumors compared with normal glands. Impaired expression of the histone methyltransferases EZH2, BMI1, and RIZ1 have been described in parathyroid tumors. Moreover, histone methyltransferases have been shown to be modulated by the oncosuppressors HIC1, MEN1, and HRPT2/CDC73 gene products that characterize tumorigenesis of parathyroid adenomas and carcinomas, respectively. The epigenetic scenario in parathyroid tumors have just began to be decoded but emerging data highlight the involvement of an embryonic gene signature in parathyroid tumor development.

Clinicopathological correlates of hyperparathyroidism

“…When compared to normal parathyroid tissue, parathyroid neoplasms were shown to have aberrant hypermethylation of tumour suppressor genes in Wnt/β-catenin signalling ( APC, SFRP1, SFRP2, SFRP4 ), cyclin D1 signalling ( CDKN2A, CDKN2B ), as well as WT1, RIZ1, RASSF1A and HIC1 141 152 205 210–213. As mentioned previously, cyclin D1 signalling plays an important role in cell cycle progression in parathyroid tissue and can be induced by Wnt/β-catenin signalling, another tumorigenesis pathway in many solid tumours 81 141 196 212 214–216 . APC, SFRP1, SFRP2 and SFRP4 genes all serve important regulatory functions in Wnt/β-catenin signalling, whereas CDKN2A and CDKN2B genes appear to regulate cyclin D1 signalling 81 141 212 214–216 .…”

“…As mentioned previously, cyclin D1 signalling plays an important role in cell cycle progression in parathyroid tissue and can be induced by Wnt/β-catenin signalling, another tumorigenesis pathway in many solid tumours 81 141 196 212 214–216 . APC, SFRP1, SFRP2 and SFRP4 genes all serve important regulatory functions in Wnt/β-catenin signalling, whereas CDKN2A and CDKN2B genes appear to regulate cyclin D1 signalling 81 141 212 214–216 . WT1 (Wilms tumour 1) encodes an important transcription factor for cellular development and survival, and mutations in WT1 have been linked to various solid tumours 81 141 210 212.…”

“…APC, SFRP1, SFRP2 and SFRP4 genes all serve important regulatory functions in Wnt/β-catenin signalling, whereas CDKN2A and CDKN2B genes appear to regulate cyclin D1 signalling 81 141 212 214–216 . WT1 (Wilms tumour 1) encodes an important transcription factor for cellular development and survival, and mutations in WT1 have been linked to various solid tumours 81 141 210 212. Similarly, RIZ1 (retinoblastoma-interacting zinc finger gene) appears to be involved in cell cycle regulation 141 205 210 212 217 .…”

Current and Future Treatments for Parathyroid Carcinoma

“…Gene alterations between benign parathyroid adenomas and parathyroid carcinomas have been identified [20]. Large-scale epigenetic studies have demonstrated repression of miRNAs in PC tissue relative to normal parathyroid glands as well, arguing that further studies in epigenetic deregulation of parathyroid tumors may provide new strategies for treatment [21].…”

HORMAD2 methylation‐mediated epigenetic regulation of gene expression in thyroid cancer

“…To date, the incidence of thyroid carcinoma is still on the rise for uncertain reasons. Some researchers have supposed that it might be associated with epigenetic events 3, 4, 5. As THCA recurrence is a common event in thyroid carcinoma patients, especially in the early stage 6, 7.…”