A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw tumour (HPT-JT) syndrome

Chiofalo, Maria Grazia; Sparaneo, Angelo; Chetta, Massimiliano; Franco, Renato; Baorda, Filomena; Cinque, Luigia; Granatiero, Matteo; D’Agruma, Leonardo; Pezzullo, Luciano; Scillitani, Alfredo; Guarnieri, Vito

doi:10.1007/s13402-014-0187-3

Cited by 18 publications

(43 citation statements)

References 17 publications

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“…All patients underwent parathyroidectomy (PTx) and followed-up at the University of Pisa (n = 28), Bologna (n = 4), IRCCS Casa Sollievo della Sofferenza Hospital San Giovanni Rotondo (n = 3). Eight cases of PC have been already published (Cetani et al 2013, Chiofalo et al 2014, Muscarella et al 2018.…”

Section: Patientsmentioning

confidence: 99%

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma

Condello

Cetani

Denaro

et al. 2021

Endocrine-Related Cancer

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Parathyroid carcinoma (PC) is one of the rarest and aggressive malignancies of the endocrine system. In some instances the histological diagnosis remains uncertain unless there is evidence of gross local invasion or secondary spread. The identification of molecular markers could improve the diagnostic accuracy of these lesions. The expression of 740 genes involved in the tumor progression processes was assessed in 8 parathyroid adenomas (PAs), 17 non-metastatic and 10 metastatic PCs using NanoString technology. Clustering analysis and Ingenuity Pathway Analysis (IPA) were interrogated to compare the gene expression profiles among the three analyzed groups and to evaluate the potential role of differentially expressed genes, respectively. The 103 differentially expressed genes between metastatic PCs and PAs are able to discriminate perfectly the two groups from a molecular point of view. The molecular signatures identified in non-metastatic PCs vs. PAs and in metastatic PCs vs. non-metastatic PCs comparisons, although with some exceptions, seem to be histotype-specific IPA reveals that hepatic fibrosis/hepatic stellate cell activation and GP6 signaling pathway are involved in malignant behavior of parathyroid tumors, whereas the activation of the HOTAIR regulatory pathway are involved in the metastatization process. Our investigation identified differentially expressed genes in non-metastatic PCs mainly encoding ECM proteins and in metastatic PCs driving endothelial-to-mesenchymal transition or encoding mediators of angiogenesis. The identified genes might be promising molecular markers potentially useful in the clinical practice for the early diagnosis and prognosis of PC.

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Section: Patientsmentioning

confidence: 99%

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma

Condello

Cetani

Denaro

et al. 2021

Endocrine-Related Cancer

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“…Similarly, invasion and negative staining of parafibromin (Figure 2A) can be seen in SaPC cases. Recent studies showed that germline CDC73 mutation is closely related to HPT-JT syndrome and other variant phenotypes of sporadic PC (58,59). There might be a connection between germline CDC73 mutation and SaPC.…”

Section: Discussionmentioning

confidence: 99%

Case Report and Systematic Review: Sarcomatoid Parathyroid Carcinoma—A Rare, Highly Malignant Subtype

Wang

et al. 2021

Front. Endocrinol.

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BackgroundParathyroid carcinoma (PC) is a rare malignancy, the incidence of which is less than 1/1 million per year. Sarcomatoid parathyroid carcinoma (SaPC) is an extremely peculiar subtype; only three cases have been reported internationally. It consists of both malignant epithelial components and sarcomatoid components (mesenchymal origin) simultaneously. This “confusing” cancer exhibits higher invasiveness, and traditional surgery does not appear to achieve the expectation, which differs significantly from that of general PC.ObjectiveTo characterize the clinicopathologic features of SaPC and explore similarities and differences between SaPC and general PC.Materials and MethodsWe collected clinical data of SaPC cases from our center and literature. The SaPC case in our center was presented. To better understand the characteristics of SaPC, we also reviewed clinical information in general PC cases from our center and literature within the last 5 years, and a systematic review was performed for further comparison.ResultsA 60-year-old woman was admitted for a neck mass and hoarseness. After the surgery, she was confirmed as SaPC and ultimately developed local recurrence at 3 months. Together with the reported cases from literature, four cases of SaPC (three cases from literature) and 203 cases of general PC (200 cases from literature) were reviewed. Both tumors showed obvious abnormalities in parathormone (PTH) level and gland size. Compared to general PC, SaPC has a later age of onset (60.50 ± 7.42 vs. 51.50 ± 8.29), relatively low levels of PTH (110.28 ± 59.32 vs. 1,156.07 ± 858.18), and a larger tumor size (6.00 ± 1.63 vs. 3.14 ± 0.70). For SaPC, all four cases were initially misdiagnosed as thyroid tumors (4/4). Spindle cell areas or transitional zones were common pathological features in SaPC cases (3/4).ConclusionSaPC is a very rare pathologic subtype of PC and appears to be much more easily misdiagnosed as a thyroid tumor. Spindle cell areas or transitional zones are highly possible to be pathological features in its sarcomatoid components. Despite many similarities, there are some differences between SaPC and general PC—SaPC does not show the obvious endocrine feature but stronger aggressiveness. Surgical treatment of SaPC does relieve life-threatening symptoms and improve quality of life even with recurrence in the short term.

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“…Previous papers report novel mutations of deletions type in c.191-192 delT, [27] and (c.1379delT/p.L460Lfs*18). [28] While novel deletion of exons 4 to 10 of CDC73 was detected in another study. [29]…”

Section: Discussionmentioning

confidence: 99%

In silicoanalysis ofCDC73gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome

Abdelmoneim¹,

Mohammed

Gadim³

et al. 2019

Preprint

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Back ground: hyperparathyroidism-jaw tumor (HPT-JT) is an autosomal dominant disorder with variable expression, with an estimated prevalence of 6.7 per 1,000 population. Genetic testing for predisposing CDC73 (HRPT2) mutations has been an important clinical advance, aimed at early detection and/or treatment to prevent advanced disease. The aim of this study is to assess the effect of SNPs on CDC73 structure and function using different bioinformatics tools. Method: Computational analysis using eight different in-silico tools including SIFT, PROVEAN, PolyPhen-2, SNAP2, PhD-SNP, SNPs&GO, PMut and Imutant were used to identify the impact on the structure and/or function of CDC73 gene that might be causing jaw tumour. Results: From (733) SNPs identified in the CDC73 gene we found that only Eleven were deleterious to the function and structure of protein and expected to cause syndrome.Conclusion: Eleven substantial genetic/molecular aberrations in CDC73 gene were identified that could serve as actionable targets for chemotherapeutic intervention in patients whose disease is no longer surgically curable.

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A novel CDC73 gene mutation in an Italian family with hyperparathyroidism-jaw tumour (HPT-JT) syndrome

Cited by 18 publications

References 17 publications

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma

Gene expression profile in metastatic and non-metastatic parathyroid carcinoma

Case Report and Systematic Review: Sarcomatoid Parathyroid Carcinoma—A Rare, Highly Malignant Subtype

In silicoanalysis ofCDC73gene revealing 11 novel SNPs associated with Jaw Tumor Syndrome

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