title: Genetic analyses of apparently sporadic pheochromocytomas: the Rotterdam experience.
abstract: Pheochromocytomas (PCCs) are neuroendocrine tumors of chromaffin tissue that produce catecholamines. They are usually located in the adrenal medulla, although in about 10% the tumors arise from extra-adrenal chromaffin tissue. The majority of PCCs arise sporadically, but PCCs occur also in the context of hereditary cancer syndromes. Familial PCC is inherited as an autosomal dominant trait alone or as a component of the multiple endocrine neoplasia Type 2 (MEN2) syndrome (RET gene), Von Hippel-Lindau (VHL) disease (VHL gene), neurofibromatosis Type 1 (NF1 gene), or familial pheochromocytoma-paraganglioma (PCC-PGL) syndrome (SDHD/B and C genes). It has been reported that 24% of apparently sporadic PCCs patients harbor germline mutations in these PCC-causing genes. We investigated the contribution of the inherited PCC-causing genes in a partly retrospectively and partly prospectively obtained series of 213 apparently sporadic PCCs. Mutation analysis was performed for RET (56 cases), VHL (136 cases), and SDHD (126 cases) and SDHB (47 cases). No germline RET mutations, six (4.4%) germline VHL mutations, two (1.5%) germline SDHD mutations, and one germline (1.6%) SDHB mutation were found. In total we found germline mutations in about 7.5% of the investigated apparently sporadic PCCs. Although 7.5% germline mutations in a series of apparently sporadic PCCs are far less than the more than 20% reported in the literature, the figure is significant enough to consider germline mutation testing for each patient with PCC.
authors.affiliation: Department of Pathology, Josephine Nefkens Institute Room Be320a, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000DR Rotterdam, The Netherlands, and Department of Pathology, University Hospital Zürich, Switzerland.
authors.forename: E
authors.initials: E
authors.lastname: Korpershoek
authors.forename: F H
authors.initials: FH
authors.lastname: Van Nederveen
authors.forename: H
authors.initials: H
authors.lastname: Dannenberg
authors.forename: B J
authors.initials: BJ
authors.lastname: Petri
authors.forename: P
authors.initials: P
authors.lastname: Komminoth
authors.forename: A
authors.initials: A
authors.lastname: Perren
authors.forename: J W
authors.initials: JW
authors.lastname: Lenders
authors.forename: A A
authors.initials: AA
authors.lastname: Verhofstad
authors.forename: W W
authors.initials: WW
authors.lastname: De Herder
authors.forename: R R
authors.initials: RR
authors.lastname: De Krijger
authors.forename: W N M
authors.initials: WN
authors.lastname: Dinjens
mesh_terms: D000310:Adrenal Gland Neoplasms / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D018095:Germ-Line Mutation; D006801:Humans; D010673:Pheochromocytoma / Q000235:genetics*; D016133:Polymerase Chain Reaction; D051096:Proto-Oncogene Proteins c-ret / Q000235:genetics; D013385:Succinate Dehydrogenase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics
chemical_list: D013385:Succinate Dehydrogenase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D051096:Proto-Oncogene Proteins c-ret; C099282:RET protein, human; C497446:VHL protein, human