Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era

Pillai, Suja; Gopalan, Vinod; Smith, Robert A.; Lam, Alfred King‐Yin

doi:10.1016/j.critrevonc.2016.01.022

Cited by 94 publications

(100 citation statements)

References 193 publications

(271 reference statements)

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“…Subsequently, however, hypermethylation of this gene was observed in 24% of the studied pheochromocytomas [249] and a decreased expression of p16 was demonstrated in 30 out of 31 tumors [249]. The available data therefore suggest the conclusion that the epigenetic state of the p16 gene and its inactivation are more significant for pheochromocytoma development than are mutations and deletions in this gene [250]. …”

Section: Genetic Classification Of Paragangliomas/pheochromo-cytomasmentioning

confidence: 99%

Molecular markers of paragangliomas/pheochromocytomas

et al. 2017

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Paragangliomas/pheochromocytomas comprise rare tumors that arise from the extra-adrenal paraganglia, with an incidence of about 2 to 8 per million people each year. Approximately 40% of cases are due to genetic mutations in at least one out of more than 30 causative genes. About 2530% of pheochromocytomas/paragangliomas develop under the conditions of a hereditary tumor syndrome a third of which are caused by mutations in the VHL gene. Together, the gene mutations in this disorder have implicated multiple processes including signaling pathways, translation initiation, hypoxia regulation, protein synthesis, differentiation, survival, proliferation, and cell growth. The present review contemplates the mutations associated with the development of pheochromocytomas/paragangliomas and their potential to serve as specific markers of these tumors and their progression. These data will improve our understanding of the pathogenesis of these tumors and likely reveal certain features that may be useful for early diagnostics, malignancy prognostics, and the determination of new targets for disease therapeutics.

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Section: Genetic Classification Of Paragangliomas/pheochromo-cytomasmentioning

confidence: 99%

Molecular markers of paragangliomas/pheochromocytomas

et al. 2017

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“…Germline and/or somatic mutations in at least eighteen different genes were described in PHEOs/PGLs (50–52) (Table 1). Each of these genes is involved in regulating key biological processes, including cell development, proliferation, growth, the cell’s ability to respond to changes in nutrients, oxygen, iron or energy, and cell transformation, including tumorigenesis and ultimately, metastasis (53–55).…”

Section: Metabolic Alterations In Pheos/pglsmentioning

confidence: 99%

Pheochromocytoma: The First Metabolic Endocrine Cancer

Jochmanová

Pacák

2016

Clinical Cancer Research

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Dysregulated metabolism is one of the key characteristics of cancer cells. The most prominent alterations are present during regulation of cell respiration, which leads to a switch from oxidative phosphorylation to aerobic glycolysis. This metabolic shift results in activation of numerous signaling and metabolic pathways supporting cell proliferation and survival. Recent progress in genetics and metabolomics allowed us to take a closer look at the metabolic changes present in pheochromocytomas and paragangliomas (PHEOs/PGLs). These neuroendocrine tumors often exhibit dysregulation of mitochondrial metabolism, which is driven by mutations in genes encoding Krebs cycle enzymes or by activation of hypoxia signaling. Present metabolic changes are involved in processes associated with tumorigenesis, invasiveness, metastasis, and resistance to various cancer therapies. In this review, we discuss the metabolic nature of PHEOs/PGLs and how unveiling the metabolic disturbances present in tumors could lead to identification of new biomarkers and personalized cancer therapies.

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“…The succinate dehydrogenase subunit B ( SDHB ) gene is one of the 15 [1] susceptibility genes that have been linked to familial paraganglioma (PGL) and pheochromocytoma (PCC) [2]. Germline mutations in this gene predispose to head and neck paragangliomas (HNPGLs), sympathetic PGLs and PCCs.…”

Section: Introductionmentioning

confidence: 99%

Calculating the optimal surveillance for head and neck paraganglioma in SDHB-mutation carriers

et al. 2016

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Germline mutations of the gene encoding succinate dehydrogenase subunit B (SDHB) predispose to head-and-neck-paraganglioma (HNPGL), sympathetic PGL, pheochromocytoma and renal cell carcinoma for which regular surveillance is required. SDHB-associated tumors harbor germline and somatic mutations, consistent with Knudson’s two-hit hypothesis. To assess the penetrance and optimal surveillance for different manifestations of SDHB mutation carriers. This study included all SDHB mutation carriers who were followed at the Department of Endocrinology at the University Medical Center of Groningen. Kaplan–Meier curves were used to assess the penetrance. Poisson process was used to assess the optimal age to start surveillance and intervals. Ninety-one SDHB-mutation carriers (38 men and 53 women) were included. Twenty-seven mutation carriers (30 %) had manifestations, with an overall penetrance 35 % at the age of 60 years. We calculated that optimal surveillance for HNPGL could start from an age of 27 years with an interval of 3.2 years. This study underscores the relatively low penetrance of disease in SDHB mutation carriers. Use of the Poisson approach provides a more accurate estimation of the age to initiate surveillance and length of intervals for HNPGL. These results may give rise to reconsider the current guidelines regarding the screening of these mutation carriers.

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Updates on the genetics and the clinical impacts on phaeochromocytoma and paraganglioma in the new era

Cited by 94 publications

References 193 publications

Molecular markers of paragangliomas/pheochromocytomas

Molecular markers of paragangliomas/pheochromocytomas

Pheochromocytoma: The First Metabolic Endocrine Cancer

Calculating the optimal surveillance for head and neck paraganglioma in SDHB-mutation carriers

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