This Article Full Text Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Email this article to a colleague Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Save to my personal folders Download to citation manager Rights & Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Amar, L. Articles by Gimenez-Roqueplo, A.-P. Search for Related Content PubMed PubMed Citation Articles by Amar, L. Articles by Gimenez-Roqueplo, A.-P. Social Bookmarking                            What's this?

Genetic Testing in Pheochromocytoma or Functional Paraganglioma

From the Université Paris-Descartes, Faculté de Médecine; Département de Génétique and Unité d’Hypertension Artérielle, Hôpital Européen Georges Pompidou, and Service des Maladies Endocrininiennes et Mètaboliques, Hôpital Cochin, Assistance Publique-Hôpitaux de Paris; L’Institut National de la Santé et de la Recherche Médicale (INSERM) U36, Collège de France; INSERM U567; Centre National de la Recherche Scientifique Unitè Mixte de Recherche 8104, Institut Cochin; Service de Cancérologie Endocrinienne and Service de Génétique, Institut Gustave Roussy, Villejuif, France; Service de Mèdecine Interne et Endocrinologie Hôpital Henri Mondor, Créteil, France; Unité d’Endocrinologie, Centre Hospitalier Universitaire (CHU) and INSERM Equipe Mixte 0105 Grenoble, France; Service de Medecine Interne et Hypertension Artérielle, CHU Rangueil; INSERM U558, 31059 Toulouse, France; Service d’Endocrinologie, CHU de Reims, Reims; Laboratoire de Génétique, Hôpital Edouard Herriot, Lyon; Service d’Endocrinologie, Hôpital de l’Hôtel-Dieu, CHU de Nantes, Nantes; Service d’Endocrinologie, CHU de Marseille, Marseille; Génétique Oncologique Ecole Pratique des Hautes Etudes-Unitè Mixte de Recherche 8125, Faculté de Médecine Paris-Sud; Service d’Urologie, Hôpital de Bicêtre, Le Kremlin-Bicêtre; Service d’Endocrinologie, CHU d’Angers, Angers; and Service d’Endocrinologie, Hôpital de l’Archet, CHU de Nice, Nice, France

Address reprint requests to Anne-Paule Gimenez-Roqueplo, MD, PhD, Département de Génétique, Hôpital Européen Georges Pompidou, 20-40 rue Leblanc, 75015 Paris, France; e-mail: anne-paule.gimenez{at}hop.egp.ap-hop-paris.fr

PURPOSE: To assess the yield and the clinical value of systematic screening of susceptibility genes for patients with pheochromocytoma (pheo) or functional paraganglioma (pgl).

PATIENTS AND METHODS: We studied 314 patients with a pheo or a functional pgl, including 56 patients having a family history and/or a syndromic presentation and 258 patients having an apparently sporadic presentation. Clinical data and blood samples were collected, and all five major pheo-pgl susceptibility genes (RET, VHL, SDHB, SDHD, and SDHC) were screened. Neurofibromatosis type 1 was diagnosed from phenotypic criteria.

RESULTS: We have identified 86 patients (27.4%) with a hereditary tumor. Among the 56 patients with a family/syndromic presentation, 13 have had neurofibromatosis type 1, and germline mutations on the VHL, RET, SDHD, and SDHB genes were present in 16, 15, nine, and three patients, respectively. Among the 258 patients with an apparently sporadic presentation, 30 (11.6%) had a germline mutation (18 patients on SDHB, nine patients on VHL, two patients on SDHD, and one patient on RET). Mutation carriers were younger and more frequently had bilateral or extra-adrenal tumors. In patients with an SDHB mutation, the tumors were larger, more frequently extra-adrenal, and malignant.

CONCLUSION: Genetic testing oriented by family/sporadic presentation should be proposed to all patients with pheo or functional pgl. We suggest an algorithm that would allow the confirmation of suspected inherited disease as well as the diagnosis of unexpected inherited disease.

Supported by the Cortico et Medullosurrenale: les Tumeurs Endocrines network, with the support of Projet Hospitalier de Recherche Clinique Grant No. AOM02068 and Grants from L’Institut National de la Santé et de la Recherche Médicale (INSERM) and the Ministère Délégué à la Recherche et aux Nouvelles Technologies; the Paraglioma network, with the support of Groupement d’Intèrêt Scientifique Institut des Maladies Rares; and Groupe des Tumeurs Endocrines, with the support of Ministère de la Santé et de la Protection Sociale. L.A. holds a fellowship from the Société Française d’Hypertension Artérielle, and A.-P.G.-R. holds a Contrat d’Interface pour Hospitaliers from INSERM.

Authors’ disclosures of potential conflicts of interest are found at the end of this article.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Facebook    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				H. J L M Timmers, A.-P. Gimenez-Roqueplo, M. Mannelli, and K. Pacak Clinical aspects of SDHx-related pheochromocytoma and paraganglioma Endocr. Relat. Cancer, June 1, 2009; 16(2): 391 - 400. [Abstract] [Full Text] [PDF]

				U. Srirangalingam, B. Khoo, L. Walker, F. MacDonald, R. H Skelly, E. George, D. Spooner, L. B Johnston, J. P Monson, A. B Grossman, et al. Contrasting clinical manifestations of SDHB and VHL associated chromaffin tumours Endocr. Relat. Cancer, June 1, 2009; 16(2): 515 - 525. [Abstract] [Full Text] [PDF]

				C. C. Boedeker, Z. Erlic, S. Richard, U. Kontny, A.-P. Gimenez-Roqueplo, A. Cascon, M. Robledo, J. M. de Campos, F. H. van Nederveen, R. R. de Krijger, et al. Head and Neck Paragangliomas in Von Hippel-Lindau Disease and Multiple Endocrine Neoplasia Type 2 J. Clin. Endocrinol. Metab., June 1, 2009; 94(6): 1938 - 1944. [Abstract] [Full Text] [PDF]

				A. A. Malik, A. E. Houni, H. Gulshad, S. Elsiah, and S. Al-Salam An interesting case of paraganglioma BMJ Case Reports, May 25, 2009; 2009(may25_1): bcr1020081150 - bcr1020081150. [Full Text]

				M. Mannelli, M. Castellano, F. Schiavi, S. Filetti, M. Giacche, L. Mori, V. Pignataro, G. Bernini, V. Giache, A. Bacca, et al. Clinically Guided Genetic Screening in a Large Cohort of Italian Patients with Pheochromocytomas and/or Functional or Nonfunctional Paragangliomas J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1541 - 1547. [Abstract] [Full Text] [PDF]

				A. Cascon, G. Pita, N. Burnichon, I. Landa, E. Lopez-Jimenez, C. Montero-Conde, S. Leskela, L. J. Leandro-Garcia, R. Leton, C. Rodriguez-Antona, et al. Genetics of Pheochromocytoma and Paraganglioma in Spanish Patients J. Clin. Endocrinol. Metab., May 1, 2009; 94(5): 1701 - 1705. [Abstract] [Full Text] [PDF]

				H. P.H. Neumann, Z. Erlic, C. C. Boedeker, L. A. Rybicki, M. Robledo, M. Hermsen, F. Schiavi, M. Falcioni, P. Kwok, C. Bauters, et al. Clinical Predictors for Germline Mutations in Head and Neck Paraganglioma Patients: Cost Reduction Strategy in Genetic Diagnostic Process as Fall-Out Cancer Res., April 15, 2009; 69(8): 3650 - 3656. [Abstract] [Full Text] [PDF]

				L. Petramala, D. Cotesta, S. Filetti, and C. Letizia Pigmented 'black' cardiac paraganglioma in a patient with a novel germ-line SDHD mutation Eur. J. Cardiothorac. Surg., January 1, 2009; 35(1): 189 - 189. [Full Text] [PDF]

				B E Baysal Clinical and molecular progress in hereditary paraganglioma J. Med. Genet., November 1, 2008; 45(11): 689 - 694. [Abstract] [Full Text] [PDF]

				G. Eisenhofer, T.-T. Huynh, A. Elkahloun, J. C. Morris, G. Bratslavsky, W. M. Linehan, Z. Zhuang, B. M. Balgley, C. S. Lee, M. Mannelli, et al. Differential expression of the regulated catecholamine secretory pathway in different hereditary forms of pheochromocytoma Am J Physiol Endocrinol Metab, November 1, 2008; 295(5): E1223 - E1233. [Abstract] [Full Text] [PDF]

				R Armstrong, M Sridhar, K L Greenhalgh, L Howell, C Jones, C Landes, J L McPartland, C Moores, P D Losty, and M Didi Phaeochromocytoma in children Arch. Dis. Child., October 1, 2008; 93(10): 899 - 904. [Abstract] [Full Text] [PDF]

				J. T. Adler, G. Y. Meyer-Rochow, H. Chen, D. E. Benn, B. G. Robinson, R. S. Sippel, and S. B. Sidhu Pheochromocytoma: Current Approaches and Future Directions Oncologist, July 1, 2008; 13(7): 779 - 793. [Abstract] [Full Text] [PDF]

				N B Kiss, J Geli, F Lundberg, C Avci, D Velazquez-Fernandez, J Hashemi, G Weber, A Hoog, T J Ekstrom, M Backdahl, et al. Methylation of the p16INK4A promoter is associated with malignant behavior in abdominal extra-adrenal paragangliomas but not pheochromocytomas Endocr. Relat. Cancer, June 1, 2008; 15(2): 609 - 621. [Abstract] [Full Text] [PDF]

				A Cascon, I Landa, E Lopez-Jimenez, A Diez-Hernandez, M Buchta, C Montero-Conde, S Leskela, L J Leandro-Garcia, R Leton, C Rodriguez-Antona, et al. Molecular characterisation of a common SDHB deletion in paraganglioma patients J. Med. Genet., April 1, 2008; 45(4): 233 - 238. [Abstract] [Full Text] [PDF]

				T. Zelinka, H. J L M Timmers, A. Kozupa, C. C Chen, J. A Carrasquillo, J. C Reynolds, A. Ling, G. Eisenhofer, I. Lazurova, K. T Adams, et al. Role of positron emission tomography and bone scintigraphy in the evaluation of bone involvement in metastatic pheochromocytoma and paraganglioma: specific implications for succinate dehydrogenase enzyme subunit B gene mutations Endocr. Relat. Cancer, March 1, 2008; 15(1): 311 - 323. [Abstract] [Full Text] [PDF]

				A. Karagiannis, D. P Mikhailidis, V. G Athyros, and F. Harsoulis Pheochromocytoma: an update on genetics and management Endocr. Relat. Cancer, December 1, 2007; 14(4): 935 - 956. [Abstract] [Full Text] [PDF]

				J. Lima, T. Feijao, A. Ferreira da Silva, I. Pereira-Castro, G. Fernandez-Ballester, V. Maximo, A. Herrero, L. Serrano, M. Sobrinho-Simoes, and G. Garcia-Rostan High Frequency of Germline Succinate Dehydrogenase Mutations in Sporadic Cervical Paragangliomas in Northern Spain: Mitochondrial Succinate Dehydrogenase Structure-Function Relationships and Clinical-Pathological Correlations J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4853 - 4864. [Abstract] [Full Text] [PDF]

				E. Thouennon, A. G. Elkahloun, J. Guillemot, A.-P. Gimenez-Roqueplo, J. Bertherat, A. Pierre, H. Ghzili, L. Grumolato, M. Muresan, M. Klein, et al. Identification of Potential Gene Markers and Insights into the Pathophysiology of Pheochromocytoma Malignancy J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4865 - 4872. [Abstract] [Full Text] [PDF]

				L. Amar, E. Baudin, N. Burnichon, S. Peyrard, S. Silvera, J. Bertherat, X. Bertagna, M. Schlumberger, X. Jeunemaitre, A.-P. Gimenez-Roqueplo, et al. Succinate Dehydrogenase B Gene Mutations Predict Survival in Patients with Malignant Pheochromocytomas or Paragangliomas J. Clin. Endocrinol. Metab., October 1, 2007; 92(10): 3822 - 3828. [Abstract] [Full Text] [PDF]

				A. Chrisoulidou, G. Kaltsas, I. Ilias, and A. B Grossman The diagnosis and management of malignant phaeochromocytoma and paraganglioma Endocr. Relat. Cancer, September 1, 2007; 14(3): 569 - 585. [Abstract] [Full Text] [PDF]

				E. Korpershoek, B.-J. Petri, F. H van Nederveen, W. N M Dinjens, A. A Verhofstad, W. W de Herder, S. Schmid, A. Perren, P. Komminoth, and R. R de Krijger Candidate gene mutation analysis in bilateral adrenal pheochromocytoma and sympathetic paraganglioma Endocr. Relat. Cancer, June 1, 2007; 14(2): 453 - 462. [Abstract] [Full Text] [PDF]

				H. J.L.M. Timmers, A. Kozupa, C. C. Chen, J. A. Carrasquillo, A. Ling, G. Eisenhofer, K. T. Adams, D. Solis, J. W.M. Lenders, and K. Pacak Superiority of Fluorodeoxyglucose Positron Emission Tomography to Other Functional Imaging Techniques in the Evaluation of Metastatic SDHB-Associated Pheochromocytoma and Paraganglioma J. Clin. Oncol., June 1, 2007; 25(16): 2262 - 2269. [Abstract] [Full Text] [PDF]

				B. Havekes, E. P. M. Corssmit, J. C. Jansen, A. G. L. van der Mey, A. H. J. T. Vriends, and J. A. Romijn Malignant Paragangliomas Associated with Mutations in the Succinate Dehydrogenase D Gene J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1245 - 1248. [Abstract] [Full Text] [PDF]

				T. Scholz, G. Eisenhofer, K. Pacak, H. Dralle, and H. Lehnert Current Treatment of Malignant Pheochromocytoma J. Clin. Endocrinol. Metab., April 1, 2007; 92(4): 1217 - 1225. [Abstract] [Full Text] [PDF]

				H. J. L. M. Timmers, A. Kozupa, G. Eisenhofer, M. Raygada, K. T. Adams, D. Solis, J. W. M. Lenders, and K. Pacak Clinical Presentations, Biochemical Phenotypes, and Genotype-Phenotype Correlations in Patients with Succinate Dehydrogenase Subunit B-Associated Pheochromocytomas and Paragangliomas J. Clin. Endocrinol. Metab., March 1, 2007; 92(3): 779 - 786. [Abstract] [Full Text] [PDF]

				J.-J. Briere, J. Favier, A.-P. Gimenez-Roqueplo, and P. Rustin Tricarboxylic acid cycle dysfunction as a cause of human diseases and tumor formation Am J Physiol Cell Physiol, December 1, 2006; 291(6): C1114 - C1120. [Abstract] [Full Text] [PDF]

				F. M. Brouwers, G. Eisenhofer, J. J. Tao, J. A. Kant, K. T. Adams, W. M. Linehan, and K. Pacak High Frequency of SDHB Germline Mutations in Patients with Malignant Catecholamine-Producing Paragangliomas: Implications for Genetic Testing J. Clin. Endocrinol. Metab., November 1, 2006; 91(11): 4505 - 4509. [Abstract] [Full Text] [PDF]

				C. Jimenez, G. Cote, A. Arnold, and R. F. Gagel Should Patients with Apparently Sporadic Pheochromocytomas or Paragangliomas be Screened for Hereditary Syndromes? J. Clin. Endocrinol. Metab., August 1, 2006; 91(8): 2851 - 2858. [Abstract] [Full Text] [PDF]