Hypermethylated in Cancer 1 (<i>HIC1</i>), a Tumor Suppressor Gene Epigenetically Deregulated in Hyperparathyroid Tumors by Histone H3 Lysine Modification

Svedlund, Jessica; Edblom, Susanne Koskinen; Márquez, Víctor E.; Åkerström, Göran; Björklund, Peyman; Westin, Gunnar

doi:10.1210/jc.2011-3136

Cited by 44 publications

(38 citation statements)

References 31 publications

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“…To our knowledge, EZH2 gene amplification presents the first genetic aberration common to a subset of parathyroid adenomas, secondary hyperplastic parathyroid glands, and parathyroid carcinomas. This further supports the possibility of a common pathway in parathyroid tumor development (Svedlund et al 2012). Interestingly, somatic EZH2 Y641N mutations were recently observed in parathyroid adenomas (Cromer et al 2012), albeit at a very low frequency (two out of 193).…”

Section: Discussionsupporting

confidence: 76%

“…The cells were harvested after 120 h and RNA/protein was extracted. The cells were transfected for 48 h and then transfected again and further incubated for 72 h (Svedlund et al 2012). …”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

“…Transient transfection of siControl and siEZH2 to the sHPT-1 parathyroid tumor cell line. Efficient knockdown of EZH2 was obtained at the mRNA (4C) and protein level (Svedlund et al 2012). ( .…”

Section: Ezh2 Is Overexpressed and The Gene Amplified In A Subset Of mentioning

confidence: 99%

“…Recently, it was demonstrated that the HIC1 tumor suppressor gene was generally underexpressed in parathyroid adenomas and secondary hyperplastic parathyroid glands and in parathyroid carcinomas (Svedlund et al 2012). It was suggested that this involved repressive histone modification H3K27me2/3 rather than DNA methylation.…”

Section: Introductionmentioning

confidence: 99%

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The histone methyltransferase EZH2, an oncogene common to benign and malignant parathyroid tumors

Svedlund

Barazeghi

Stålberg

et al. 2013

Endocrine-Related Cancer

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Primary hyperparathyroidism (pHPT) resulting from parathyroid tumors is a common endocrine disorder with incompletely understood etiology. In renal failure, secondary hyperparathyroidism (sHPT) occurs with multiple tumor development as a result of calcium and vitamin D regulatory disturbance. The aim of this study was to investigate a potential role of the histone 3 lysine 27 methyltransferase EZH2 in parathyroid tumorigenesis. Parathyroid tumors from patients with pHPT included adenomas and carcinomas. Hyperplastic parathyroid glands from patients with HPT secondary to uremia and normal parathyroid tissue specimens were included in this study. Quantitative RT-PCR, western blotting, bisulfite pyrosequencing, colony formation assay, and RNA interference were used. EZH2 was overexpressed in a subset of the benign and in all malignant parathyroid tumors as determined by quantitative RT-PCR and western blotting analyses. Overexpression was explained by EZH2 gene amplification in a large fraction of tumors. EZH2 depletion by RNA interference inhibited sHPT-1 parathyroid cell line proliferation as determined by tritiumthymidine incorporation and colony formation assays. EZH2 depletion also interfered with the Wnt/b-catenin signaling pathway by increased expression of growth-suppressive AXIN2, a negative regulator of b-catenin stability. Indeed, EZH2 contributed to the total level of aberrantly accumulated transcriptionally active (nonphosphoylated) b-catenin in the parathyroid tumor cells. To our knowledge EZH2 gene amplification presents the first genetic aberration common to parathyroid adenomas, secondary hyperplastic parathyroid glands, and parathyroid carcinomas. This supports the possibility of a common pathway in parathyroid tumor development.

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Section: Discussionsupporting

confidence: 76%

“…The cells were harvested after 120 h and RNA/protein was extracted. The cells were transfected for 48 h and then transfected again and further incubated for 72 h (Svedlund et al 2012). …”

Section: Cell Culture and Transfectionmentioning

confidence: 99%

Section: Ezh2 Is Overexpressed and The Gene Amplified In A Subset Of mentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

The histone methyltransferase EZH2, an oncogene common to benign and malignant parathyroid tumors

Svedlund

Barazeghi

Stålberg

et al. 2013

Endocrine-Related Cancer

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“…Promoter hypermethylation of the tumor suppressor gene, hypermethylated in cancer 1 (HIC1), has been shown to be frequently repressed in parathyroid cancer (Svedlund et al 2012). A growth-regulatory role has been assigned to HIC1 in the parathyroid glands and it is suggested that its downmodulation might be an early event in tumoral transformation, where, in addition to DNA methylation, other epigenetic mechanisms such as repressive histone marks (H3K27me2/3) play a part (Table 1).…”

Section: Sporadic Endocrine Diseasesmentioning

confidence: 99%

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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Hypermethylated in Cancer 1 (HIC1), a Tumor Suppressor Gene Epigenetically Deregulated in Hyperparathyroid Tumors by Histone H3 Lysine Modification

Cited by 44 publications

References 31 publications

The histone methyltransferase EZH2, an oncogene common to benign and malignant parathyroid tumors

The histone methyltransferase EZH2, an oncogene common to benign and malignant parathyroid tumors

Epigenetic alterations in endocrine-related cancer

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

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