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The Rotterdam Experience
a Department of Pathology, Josephine Nefkens Institute and Department of Internal Medicine, Erasmus MC - University Medical Center Rotterdam, Rotterdam, the Netherlands b Department of Pathology, University Hospital Zürich, Switzerland c Departments of Pathology and Internal Medicine, Radboud University Nijmegen Medical Center, Nijmegen, the Netherlands
Key Words: sporadic • germline • mutations • pheochromocytoma • VHL • RET • SDHB • SDHD
Address for correspondence: Winand N. M. Dinjens, Department of Pathology, Josephine Nefkens Institute Room Be320a, Erasmus MC, University Medical Center Rotterdam, P.O. Box 1738, 3000DR Rotterdam, The Netherlands. Voice: +31-10-4087946; fax: 0031-10-4089487. e-mail: w.dinjens{at}erasmusmc.nl
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.
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