Clinically Guided Genetic Screening in a Large Cohort of Italian Patients with Pheochromocytomas and/or Functional or Nonfunctional Paragangliomas
Massimo Mannelli,Maurizio Castellano,Francesca Schiavi,Sebastiano Filetti,M. Giacchè,Luigi Mori,Viviana Pignataro,G. P. Bernini,Valentino Giachè,Alessandra Bacca,Bernadette Biondi,Giovanni Corona,Giuseppe Di Trapani,Erika Grossrubatscher,Giuseppe Reimondo,Giorgio Arnaldi,Gilberta Giacchetti,Franco Veglio,Paola Loli,Annamaria Colao,Maria Rosaria Ambrosio,Massimo Terzolo,Claudio Letizia,Tonino Ercolino,Giuseppe Opocher +24 more
TLDR
The frequency of the hereditary forms of pheochromocytoma/paraganglioma varies depending on the family history and the clinical presentation, and which genes should be screened first is suggested.Abstract:
Purpose: The aim of the study was to define the frequency of hereditary forms and the genotype/phenotype correlations in a large cohort of Italian patients with pheochromocytomas and/or functional or nonfunctional paragangliomas. Design: We examined 501 consecutive patients with pheochromocytomas and/or paragangliomas (secreting or nonsecreting). Complete medical and family histories, as well as the results of clinical, laboratory, and imaging studies, were recorded in a database. Patients were divided into different groups according to their family history, the presence of lesions outside adrenals/paraganglia considered syndromic for VHL disease, MEN2, and NF1, and the number and types of pheochromocytomas and/or paragangliomas. Germ-line mutations in known susceptibility genes were investigated by gene sequencing (VHL, RET, SDHB, SDHC, SDHD) or diagnosed according to phenotype (NF1). In 160 patients younger than 50 yr with a wild-type profile, multiplex ligation-dependent probe amplification assays were...read more
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Journal ArticleDOI
Pheochromocytoma and paraganglioma: An endocrine society clinical practice guideline
Jacques W.M. Lenders,Quan-Yang Duh,Graeme Eisenhofer,Anne Paule Gimenez-Roqueplo,Stefan K.G. Grebe,Mohammad Hassan Murad,Mitsuhide Naruse,Karel Pacak,William F. Young +8 more
TL;DR: This evidence-based guideline recommends minimally invasive adrenalectomy for most pheochromocytomas with open resection for most paragangliomas and suggests personalized management with evaluation and treatment by multidisciplinary teams with appropriate expertise to ensure favorable outcomes.
Journal ArticleDOI
Exome sequencing identifies MAX mutations as a cause of hereditary pheochromocytoma
Iñaki Comino-Méndez,Francisco Javier Gracia-Aznarez,Francesca Schiavi,Iñigo Landa,Luis J Leandro-García,Rocío Letón,Emiliano Honrado,Rocío Ramos-Medina,Daniela Caronia,Guillermo Pita,Álvaro Gómez-Graña,Aguirre A. de Cubas,Lucía Inglada-Pérez,Agnieszka Maliszewska,Elisa Taschin,Sara Bobisse,Giuseppe Pica,Paola Loli,Rafael Hernández-Lavado,José Ángel Díaz,Mercedes Gómez-Morales,Anna González-Neira,Giovanna Roncador,Cristina Rodríguez-Antona,Javier Benitez,Massimo Mannelli,Giuseppe Opocher,Mercedes Robledo,Alberto Cascón +28 more
TL;DR: The involvement of the MYC-MAX-MXD1 network in the development and progression of neural crest cell tumors is supported and the lack of functional MAX in rat PCC (PC12) cells is supported, which suggests that loss of MAX function is correlated with metastatic potential.
Journal ArticleDOI
SDH mutations in cancer.
TL;DR: An overview of genetics, clinical and molecular progress recently performed in understanding the basis of HPGL/PCC tumorigenesis is reported.
Journal ArticleDOI
Tumor risks and genotype–phenotype–proteotype analysis in 358 patients with germline mutations in SDHB and SDHD
Christopher J. Ricketts,Julia R. Forman,Eleanor Rattenberry,Nicola Bradshaw,Fiona Lalloo,Louise Izatt,Trevor Cole,Ruth Armstrong,V.K. Ajith Kumar,Patrick J. Morrison,A. Brew Atkinson,Fiona Douglas,Fiona Douglas,Steve Ball,Jackie Cook,Umasuthan Srirangalingam,Pip Killick,Gail Kirby,Simon Aylwin,Emma R. Woodward,D. Gareth Evans,Shirley Hodgson,V Murday,Shern L. Chew,John M. C. Connell,Tom L. Blundell,Fiona Macdonald,Eamonn R. Maher +27 more
TL;DR: Analysis of the largest cohort of SDHB/D mutation carriers has enhanced estimates of penetrance and tumor risk and supports in silicon protein structure prediction analysis for functional assessment of mutations.
Journal ArticleDOI
Genetics and clinical characteristics of hereditary pheochromocytomas and paragangliomas
TL;DR: 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 syndrome associated with a smaller fraction of PCCs/PGLs, such as Carney triad.
References
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Mutations in SDHD, a Mitochondrial Complex II Gene, in Hereditary Paraganglioma
Bora E. Baysal,Robert E. Ferrell,Joan E. Willett-Brozick,Elizabeth C. Lawrence,David Myssiorek,Anne Bosch,Andel G. L. van der Mey,Peter E.M. Taschner,Wendy S. Rubinstein,Eugene N. Myers,Charles W. Richard,Cees J. Cornelisse,Peter Devilee,Bernie Devlin +13 more
TL;DR: Analysis of families carrying the PGL1 gene revealed germ line mutations in the SDHD gene, which indicates that mitochondria play an important role in the pathogenesis of certain tumors and that cybS plays a role in normal CB physiology.
Journal Article
Neurofibromatosis. Conference statement, National Institute of Health development conference
Journal ArticleDOI
Germ-line mutations in nonsyndromic pheochromocytoma.
Hartmut P. H. Neumann,Birke Bausch,Sarah R. McWhinney,Bernhard U. Bender,Oliver Gimm,Gerlind Franke,Joerg Schipper,Joachim Klisch,Carsten Altehoefer,Klaus Zerres,Andrzej Januszewicz,Wendy M. Smith,Robin Munk,Tanja Manz,Sven Glaesker,Thomas W. Apel,Markus Treier,Martin Reineke,Martin K. Walz,Cuong Hoang-Vu,Michael Brauckhoff,Andreas Klein-Franke,Peter Klose,Heinrich Schmidt,Margarete Maier-Woelfle,Mariola Pęczkowska,Cesary Szmigielski,Charis Eng +27 more
TL;DR: Almost one fourth of patients with apparently sporadic pheochromocytoma may be carriers of mutations; routine analysis for mutations of RET, VHL, SDHD, and SDHB is indicated to identify pheosene-associated syndromes that would otherwise be missed.
Journal ArticleDOI
Gene Mutations in the Succinate Dehydrogenase Subunit SDHB Cause Susceptibility to Familial Pheochromocytoma and to Familial Paraganglioma
Dewi Astuti,Farida Latif,Ashraf Dallol,Patricia L. M. Dahia,Fiona Douglas,Emad George,Filip Sköldberg,Eystein S. Husebye,Charis Eng,Eamonn R. Maher +9 more
TL;DR: The link between mitochondrial dysfunction and tumorigenesis is extended and suggest that germline SDHB mutations are an important cause of pheochromocytoma susceptibility.
Journal ArticleDOI
Mutations in SDHC cause autosomal dominant paraganglioma, type 3.
Stephan Niemann,Ulrich Müller +1 more
TL;DR: Nonchromaffin paragangliomas are usually benign, neural-crest–derived, slow-growing tumours of parasympathetic ganglia that are transmitted as autosomal dominant traits with incomplete and age-dependent penetrance.
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