New role for ZFX in oncogenesis

Arnold, Andrew; Soong, Chen-Pang

doi:10.4161/15384101.2014.980693

Cited by 11 publications

(5 citation statements)

References 8 publications

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“…Epigenetic alterations of CDKIs (CDKN2A, CDKN2B) have also been reported in parathyroid tumors (99,100,103,128,163). recently, recurrent mutation of ZFX, a putative protooncogene thought to be a downstream target of cyclin D1, has also been found in a subset of parathyroid adenomas (~5%) (154,155). activating mutations in RET protooncogene (10q11.2), a putative inducer of cyclin D1 signalling, is also described in some parathyroid tumors from patients with multiple endocrine neoplasia type 2a (MEN-2a) (11,100,124,145,(164)(165)(166).…”

Section: Cyclin D1 Signalling and Parathyroid Tumorigenesismentioning

confidence: 99%

“…In contrast to CaSr signalling, cyclin D1 signalling is involved in cell cycle progression (41,55,100,131,132,(150)(151)(152)(153). aberrant activation of cyclin D1 signalling has been well described in a large subset of parathyroid tumors, implicating altered CCND1/PRAD1, CDKIs, and ZFX genes (2,11,28,41,55,100,131,132,(150)(151)(152)(153)(154)(155). CCND1/PRAD1 (11q13) is a proto-oncogene encoding the cyclin D1 protein, a holoenzyme thought to inactivate the tumor-suppressor retinoblastoma protein (rb) (41,55,100,131,132,(150)(151)(152)(153)156).…”

Section: Cyclin D1 Signalling and Parathyroid Tumorigenesismentioning

confidence: 99%

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Parathyroid carcinoma: diagnosis and clinical implications

Duan¹,

Mete²

2015

TJPATH

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Parathyroid carcinoma is a rare type of endocrine cancer, with significant morbidity and mortality associated with parathyroid hormone (PTH)-mediated hypercalcemia. Concerning clinical features for parathyroid cancer include severe hypercalcemia (albumin-corrected calcium > 3 mmol/L), a palpable neck mass ( > 3 cm), 3rd/2nd generation PTH assay ratio ( > 1), and intraoperative suspicion of local invasion or regional metastasis. A definite diagnosis of malignancy is rendered when a parathyroid tumor presents one of the following clinicopathological features: (1) vascular invasion, (2) perineural invasion, (3) gross invasion into adjacent anatomical structures, and/or (4) metastasis. In difficult cases, the use of ancillary biomarkers is critical to establish an accurate diagnosis. Recent advances in molecular pathology have uncovered the important role of CDC73/HRPT2, a tumor suppressor gene deregulated in parathyroid carcinomas. Loss of nuclear and/or nucleolar expression of parafibromin (the gene product of CDC73/HRPT2) is now regarded as a diagnostic, prognostic and predictive biomarker for parathyroid carcinoma. Furthermore, over 15-20% of seemingly sporadic parathyroid carcinomas have underlying germline CDC73/HRPT2 mutations. As a result, many centers have integrated the use of ancillary biomarkers, notably parafibromin staining, in their routine practise. Radical surgery with en bloc resection has emerged as a primary treatment modality in parathyroid cancer, achieving cure in some patients. However, in those with inoperable disease, there remains a dire need for new therapies, as current treatments are largely ineffective. This review provides an update on the current knowledge of parathyroid carcinoma and highlights its exciting changes in endocrine practice.

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Section: Cyclin D1 Signalling and Parathyroid Tumorigenesismentioning

confidence: 99%

Section: Cyclin D1 Signalling and Parathyroid Tumorigenesismentioning

confidence: 99%

Parathyroid carcinoma: diagnosis and clinical implications

Duan¹,

Mete²

2015

TJPATH

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“…Their observations in the discovery cohort were confirmed by direct sequencing of tumor DNA from an additional validation set comprised of 111 parathyroid adenomas [112]. The mutant ZFX alleles detected in parathyroid tumors likely act as oncogenes [113]. Such somatically acquired ZFX mutations in parathyroid tumors may be uncommon, however, since an independent mutational analysis of 23 sporadic parathyroid carcinomas and 57 adenomas failed to identify any pathogenic ZFX variants [111].…”

Section: Other Genes Involved In Parathyroid Tumorigenesismentioning

confidence: 81%

Familial Syndromes of Primary Hyperparathyroidism

Simonds¹

2021

Mineral Deficiencies - Electrolyte Disturbances, Genes, Diet and Disease Interface

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Regulation of serum calcium in vertebrates is maintained by the actions of the parathyroid glands working in concert with vitamin D and critical target tissues that include the renal tubules, the small intestine, and bone cells. The parathyroid glands release parathyroid hormone (PTH) into the systemic circulation as is required in order to maintain the serum calcium concentration within a narrow physiologic range. Excessive secretion of PTH from one or more abnormal parathyroid glands however results in primary hyperparathyroidism (HPT), a metabolic disease typically associated with abnormally elevated serum calcium. Although HPT is typically a sporadic disease, it can represent a manifestation of an inherited syndrome. Many sporadic parathyroid tumors result from inactivating mutations in tumor suppressor genes that were first discovered by the analysis of genomic DNA from patients with HPT as part of an inherited syndrome. Somatic and inherited alterations in DNA encoding proto-oncogenes can also cause parathyroid neoplasia. Two promising future approaches for the discovery of novel genes pertinent to parathyroid tumor development are the analysis of acquired genetic alterations in DNA isolated from parathyroid tumors and the investigation of familial HPT in kindreds lacking germline mutation in the known genes predisposing to HPT.

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“…Somatic mutations in the putative parathyroid proto-oncogene ZFX, a member of the Krüppel associated box domain-containing zinc finger protein transcription factors, were identified by WES analysis of DNA extracted from 19 parathyroid adenomas and matching germline DNA, with confirmation by direct sequencing of tumor DNA from an additional validation cohort of 111 parathyroid adenomas [110]. The somatically acquired mutant ZFX alleles detected in parathyroid tumors likely act as oncogenes [111]. Mutational analysis of 23 sporadic parathyroid carcinomas, 12 atypical and 45 typical adenomas from an Italian cohort failed to identify any pathogenic ZFX variants, however, suggesting such mutation in parathyroid tumors may be uncommon [109].…”

Section: Other Genes Implicated In the Pathophysiology Of Parathyroidmentioning

confidence: 99%

Clinical and Molecular Genetics of Primary Hyperparathyroidism

Simonds

2020

Horm Metab Res

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Calcium homeostasis is maintained by the actions of the parathyroid glands, which release parathyroid hormone into the systemic circulation as necessary to maintain the serum calcium concentration within a tight physiologic range. Excessive secretion of parathyroid hormone from one or more neoplastic parathyroid glands, however, causes the metabolic disease primary hyperparathyroidism (HPT) typically associated with hypercalcemia. Although the majority of cases of HPT are sporadic, it can present in the context of a familial syndrome. Mutations in the tumor suppressor genes discovered by the study of such families are now recognized to be pathogenic for many sporadic parathyroid tumors. Inherited and somatic mutations of proto-oncogenes causing parathyroid neoplasia are also known. Future investigation of somatic changes in parathyroid tumor DNA and the study of kindreds with HPT yet lacking germline mutation in the set of genes known to predispose to HPT represent two avenues likely to unmask additional novel genes relevant to parathyroid neoplasia.

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New role for ZFX in oncogenesis

Cited by 11 publications

References 8 publications

Parathyroid carcinoma: diagnosis and clinical implications

Parathyroid carcinoma: diagnosis and clinical implications

Familial Syndromes of Primary Hyperparathyroidism

Clinical and Molecular Genetics of Primary Hyperparathyroidism

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