Genetic Testing for Pheochromocytoma

Karásek, David; Fryšák, Zdeněk; Pacák, Karel

doi:10.1007/s11906-010-0151-1

Cited by 53 publications

(49 citation statements)

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“…In light of the cases reviewed herein and further publications (Cascon et al 2009a, Petri et al 2009, Karasek et al 2010, Waguespack et al 2010, we propose a genetic testing algorithm that may constitute a guide for a time-and cost-efficient genetic screening (Fig. 5).…”

Section: Discussionmentioning

confidence: 99%

“…5). Measurements of plasma concentrations of catecholamines and their metabolites (Karasek et al 2010, Eisenhofer et al 2011) and SDHB and SDHA immunohistochemistry (van Nederveen et al 2009, Gill et al 2010) may be valuable tools to further guide the order of genetic testing and thereby reduce the costs. Knowledge of the clinical features linked to different hereditary backgrounds can be crucial for decision making regarding treatment and surveillance.…”

Section: Discussionmentioning

confidence: 99%

“…Augmentation of c-Jun activity induced by menin , Ikeo et al 2004) and blocking of c-Jun upregulation by MYC (Vaque et al 2008) may suggest potential roles for MEN1 and MAX mutations in this context, although it remains to be investigated. Karasek et al (2010) for definitions) and immunohistochemical staining for SDHB (perhaps in combination with SDHA) can, when available, be used as a complement guide to what genes should be prioritized. Owing to the large size of the NF1 gene and the usually very typical and early-onset skin lesions and other characteristics in patients with NF1 syndrome, NF1 mutations are normally deduced on the basis of phenotype.…”

Section: Developmental Apoptosis Of Neuronal Precursor Cellsmentioning

confidence: 99%

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Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas

Welander¹,

Söderkvist²,

Gimm³

2011

Endocrine-Related Cancer

315

321

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Pheochromocytomas (PCCs) and paragangliomas (PGLs) are rare neuroendocrine tumors of the adrenal glands and the sympathetic and parasympathetic paraganglia. They can occur sporadically or as a part of different hereditary tumor syndromes. About 30% of PCCs and PGLs are currently believed to be caused by germline mutations and several novel susceptibility genes have recently been discovered. The clinical presentation, including localization, malignant potential, and age of onset, varies depending on the genetic background of the tumors. By reviewing more than 1700 reported cases of hereditary PCC and PGL, a thorough summary of the genetics and clinical features of these tumors is given, both as part of the classical syndromes such as multiple endocrine neoplasia type 2 (MEN2), von Hippel-Lindau disease, neurofibromatosis type 1, and succinate dehydrogenase-related PCC-PGL and within syndromes associated with a smaller fraction of PCCs/PGLs, such as Carney triad, Carney-Stratakis syndrome, and MEN1. The review also covers the most recently discovered susceptibility genes including KIF1Bb, EGLN1/PHD2, SDHAF2, TMEM127, SDHA, and MAX, as well as a comparison with the sporadic form. Further, the latest advances in elucidating the cellular pathways involved in PCC and PGL development are discussed in detail. Finally, an algorithm for genetic testing in patients with PCC and PGL is proposed.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Section: Developmental Apoptosis Of Neuronal Precursor Cellsmentioning

confidence: 99%

See 1 more Smart Citation

Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas

Welander¹,

Söderkvist²,

Gimm³

2011

Endocrine-Related Cancer

315

321

View full text Add to dashboard Cite

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“…Most of these neuroendocrine tumors occur sporadically, but w25% result from germline mutations in seven genes identified to date, i.e. the oncogene RET or the oncosuppressors von HippelLindau (VHL), neurofibromatosis 1 (NF1), genes associated with the succinate dehydrogenase complex (SDHA, -B, -C, -D, and SDHAF2), and also the novel tumor suppressor gene TMEM127 (Karasek et al 2010). In w10% of cases, pheochromocytomas can present as or subsequently develop into malignant disease with a poor prognosis (Chrisoulidou et al 2007).…”

Section: Introductionmentioning

confidence: 99%

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Guillemot¹,

Thouennon²,

Guérin³

et al. 2012

Journal of Molecular Endocrinology

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We have previously demonstrated that measurement of tissue concentrations of the secretogranin II (SgII or SCG2 as listed in the HUGO database)-derived peptide EM66 may help to discriminate between benign and malignant pheochromocytomas and that EM66 represents a sensitive plasma marker of pheochromocytomas. Here, we investigated the gene expression and protein production of SgII in 13 normal adrenal glands, and 35 benign and 16 malignant pheochromocytomas with the goal to examine the molecular mechanisms leading to the marked variations in the expression of EM66 in tumoral chromaffin tissue. EM66 peptide levels were 16-fold higher in benign than in malignant pheochromocytomas and had an area under the receiver-operating characteristic curve of 0 . 95 for the distinction of benign and malignant tumors. Q-PCR experiments indicated that the SgII gene was significantly underexpressed in malignant tumors compared with benign tumors. Western blot analysis using antisera directed against SgII and SgII-derived fragments revealed lower SgII protein and SgII-processing products in malignant tumors. Western blot also showed that low p-cAMP-responsive element-binding (CREB) concentrations seemed to be associated with the malignant status. In addition, the prohormone convertase PC1 and PC2 genes and proteins were overexpressed in benign pheochromocytomas compared with malignant pheochromocytomas. Low concentrations of EM66 found in malignant tumors are associated with reduced expression and production of SgII and SgII-derived peptides that could be ascribed to a decrease in SgII gene transcription, probably linked to p-CREB down-regulation, and to lower PC levels. These findings highlight the mechanisms leading to lower concentrations of EM66 in malignant pheochromocytoma and strengthen the notion that this peptide is a suitable marker of this neuroendocrine tumor.

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“…Paragangliomas are characterized by a high frequency of hereditary forms (overall, 25%) with a propensity for multifocal disease (1)(2)(3)(4)(5). Most often, paragangliomas are benign and progress slowly, but metastases may occur in about 10% of patients.…”

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confidence: 99%

Modern Nuclear Imaging for Paragangliomas: Beyond SPECT

et al. 2012

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Learning Objectives: On successful completion of this activity, participants should be able to describe (1) the best nuclear imaging procedures to detect pheochromocytomas/paragangliomas according to the clinical situation (e.g., sporadic vs. hereditary; primary vs. metastatic; sympathetic vs. parasympathetic) and (2) the differences in the phenotypic information obtained by various PET tracers.Financial Disclosure: The authors of this article have indicated no relevant relationships that could be perceived as a real or apparent conflict of interest. CME Credit: SNM is accredited by the Accreditation Council for Continuing Medical Education (ACCME) to sponsor continuing education for physicians. SNM designates each JNM continuing education article for a maximum of 1.0 AMA PRA Category 1 Credit. Physicians should claim only credit commensurate with the extent of their participation in the activity.For CE credit, participants can access this activity through the SNM Web site (http://www.snm.org/ce_online) through February 2013.Paragangliomas are rare neuroendocrine tumors that may arise anywhere along the paraganglial system, with a high frequency of hereditary forms or multifocal disease. Most often, paragangliomas are benign and progress slowly, but metastases may occur in about 10% of patients. In this respect, nuclear imaging in combination with anatomic imaging may be required to fully delineate the extent of the disease. PET has been increasingly used in imaging paraganglioma, paralleled by great efforts toward the development of new tracers. Recent data indicate that the choice of PET tracers should be tailored to tumor localization and to the patient's genetic status. This article provides insight into the many PET radiotracers that are currently available and others that are still only under research and guides clinicians toward appropriate use in relation to genetic carrier status. In addition, this article provides nuclear medicine physicians with the background knowledge required for understanding relationships between imaging phenotypes and molecular genetics.

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Genetic Testing for Pheochromocytoma

Cited by 53 publications

References 49 publications

Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas

Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas

Differential expression and processing of secretogranin II in relation to the status of pheochromocytoma: implications for the production of the tumoral marker EM66

Modern Nuclear Imaging for Paragangliomas: Beyond SPECT

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