Global and gene-specific promoter methylation analysis in primary hyperparathyroidism

Sulaiman, Luqman; Juhlin, C. Christofer; Nilsson, Inga-Lena; Fotouhi, Omid; Larsson, Catharina; Hashemi, Jamileh

doi:10.4161/epi.24823

Cited by 52 publications

(48 citation statements)

References 48 publications

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“…Over the past few years, DNA methylation and microRNA profiling studies have uncovered important epigenetic alterations in sporadic parathyroid tumours 141 152 205 210–212. 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.…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

“…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 .…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

“…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 . RASSF1A (Ras association domain family 1 isoform A; 3p21) is a component in the Ras signalling pathway and has been shown to suppress cyclin D1 218–220 .…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

“…Additional molecular alterations identified in parathyroid carcinomas ( CCND1, CDKIs, MEN1, EZH2, RIZ1, RASSF1, GSK3B, WT1, APC, SFRP, HIC1 , CaSR, VDR and microRNA deregulation) are non-specific and can also occur in parathyroid adenomas 31 42 43 81 82 141 151 164 205 210 211 212 216 217 219. Of note, MEN1 mutations, one of the key drivers in parathyroid adenomas (20–40%), appear to be less frequent in carcinomas (10–15%) 31 42 81 141 225–229.…”

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

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Clinicopathological correlates of hyperparathyroidism

2015

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Hyperparathyroidism is a common endocrine disorder with potential complications on the skeletal, renal, neurocognitive and cardiovascular systems. While most cases (95%) occur sporadically, about 5% are associated with a hereditary syndrome: multiple endocrine neoplasia syndromes (MEN-1, MEN-2A, MEN-4), hyperparathyroidism-jaw tumour syndrome (HPT-JT), familial hypocalciuric hypercalcaemia (FHH-1, FHH-2, FHH-3), familial hypercalciuric hypercalcaemia, neonatal severe hyperparathyroidism and isolated familial hyperparathyroidism. Recently, molecular mechanisms underlying possible tumour suppressor genes (MEN1, CDC73/HRPT2, CDKIs, APC, SFRPs, GSK3β, RASSF1A, HIC1, RIZ1, WT1, CaSR, GNA11, AP2S1) and proto-oncogenes (CCND1/PRAD1, RET, ZFX, CTNNB1, EZH2) have been uncovered in the pathogenesis of hyperparathyroidism. While bi-allelic inactivation of CDC73/HRPT2 seems unique to parathyroid malignancy, aberrant activation of cyclin D1 and Wnt/β-catenin signalling has been reported in benign and malignant parathyroid tumours. Clinicopathological correlates of primary hyperparathyroidism include parathyroid adenoma (80–85%), hyperplasia (10–15%) and carcinoma (<1–5%). Secondary hyperparathyroidism generally presents with diffuse parathyroid hyperplasia, whereas tertiary hyperparathyroidism reflects the emergence of autonomous parathyroid hormone (PTH)-producing neoplasm(s) from secondary parathyroid hyperplasia. Surgical resection of abnormal parathyroid tissue remains the only curative treatment in primary hyperparathyroidism, and parathyroidectomy specimens are frequently encountered in this setting. Clinical and biochemical features, including intraoperative PTH levels, number, weight and size of the affected parathyroid gland(s), are crucial parameters to consider when rendering an accurate diagnosis of parathyroid proliferations. This review provides an update on the expanding knowledge of hyperparathyroidism and highlights the clinicopathological correlations of this prevalent disease.

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Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

Section: Pathogenesis and Molecular Genetics Of Hptmentioning

confidence: 99%

See 2 more Smart Citations

Clinicopathological correlates of hyperparathyroidism

2015

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“…Similar to thyroid tumors, promoter hypermethylation in RASSSF1 and APC genes has also been described in parathyroid carcinomas (Juhlin et al 2010, Sulaiman et al 2013. A differential methylation pattern compared with normal parathyroid tissue was observed in parathyroid adenomas (367 genes were significantly altered) and parathyroid carcinomas (175 genes) (Starker et al 2011).…”

Section: Sporadic Endocrine Diseasesmentioning

confidence: 83%

Epigenetic alterations in endocrine-related cancer

Rodríguez-Rodero¹,

Delgado²,

Fernández³

et al. 2014

Endocrine-Related Cancer

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Aberrant epigenetics is a hallmark of cancer, and endocrine-related tumors are no exception. Recent research has been identifying an ever-growing number of epigenetic alterations in both genomic DNA methylation and histone post-translational modification in tumors of the endocrine system. Novel microarray and ultra-deep sequencing technologies have allowed the identification of genome-wide epigenetic patterns in some tumor types such as adrenocortical, parathyroid, and breast carcinomas. However, in other cancer types, such as the multiple endocrine neoplasia syndromes and thyroid cancer, tumor information is limited to candidate genes alone. Future research should fill this gap and deepen our understanding of the functional role of these alterations in cancer, as well as defining their possible clinical uses.

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Molecular genetics of syndromic and non-syndromic forms of parathyroid carcinoma

2017

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Parathyroid carcinoma (PC) may occur as part of a complex hereditary syndrome or an isolated (i.e., non‐syndromic) non‐hereditary (i.e., sporadic) endocrinopathy. Studies of hereditary and syndromic forms of PC, which include the hyperparathyroidism‐jaw tumor syndrome (HPT‐JT), multiple endocrine neoplasia types 1 and 2 (MEN1 and MEN2), and familial isolated primary hyperparathyroidism (FIHP), have revealed some genetic mechanisms underlying PC. Thus, cell division cycle 73 (CDC73) germline mutations cause HPT‐JT, and CDC73 mutations occur in 70% of sporadic PC, but in only ∼2% of parathyroid adenomas. Moreover, CDC73 germline mutations occur in 20%–40% of patients with sporadic PC and may reveal unrecognized HPT‐JT. This indicates that CDC73 mutations are major driver mutations in the etiology of PCs. However, there is no genotype–phenotype correlation and some CDC73 mutations (e.g., c.679_680insAG) have been reported in patients with sporadic PC, HPT‐JT, or FIHP. Other genes involved in sporadic PC include germline MEN1 and rearranged during transfection (RET) mutations and somatic alterations of the retinoblastoma 1 (RB1) and tumor protein P53 (TP53) genes, as well as epigenetic modifications including DNA methylation and histone modifications, and microRNA misregulation. This review summarizes the genetics and epigenetics of the familial syndromic and non‐syndromic (sporadic) forms of PC.

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Global and gene-specific promoter methylation analysis in primary hyperparathyroidism

Cited by 52 publications

References 48 publications

Clinicopathological correlates of hyperparathyroidism

Clinicopathological correlates of hyperparathyroidism

Epigenetic alterations in endocrine-related cancer

Molecular genetics of syndromic and non-syndromic forms of parathyroid carcinoma

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