Premium
Genetic Testing in Pheochromocytoma
Author(s) -
BORNSTEIN STEFAN R.,
GIMENEZROQUEPLO ANNEPAULE
Publication year - 2006
Publication title -
annals of the new york academy of sciences
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.712
H-Index - 248
eISSN - 1749-6632
pISSN - 0077-8923
DOI - 10.1196/annals.1353.010
Subject(s) - sdhb , sdhd , pheochromocytoma , paraganglioma , multiple endocrine neoplasia type 2 , germline mutation , genetic testing , sdha , medicine , germline , genetics , genetic counseling , bioinformatics , cancer research , mutation , gene , biology , pathology , gene expression
Hereditary pheochromocytomas and paragangliomas are caused by germline mutations in syndrome‐associated genes. This includes multiple endocrine neoplasia Type 2 (MEN 2) caused by mutations in the RET proto ‐ oncogene, von Hippel–Lindau (VHL) syndrome due to mutations of the VHL gene, neurofibromatosis Type I (NF1) caused by mutations of the NF1 gene, and pheochromocytoma/paraganglioma syndromes due to mutations in genes encoding the succinate dehydrogenase subunits D ( SDHD ) and B ( SDHB ). At the First International Symposium on Pheochromocytoma (ISP2005) organized by the National Institutes of Health, a panel of specialist clinicians and scientists from around the world addressed the topic of genetic testing in pheochromocytoma patients. This review summarizes the discussions and conclusions of the panel and provides a recommendation for evidence‐based management of genetic testing in these patients and their families. A pragmatic algorithm is presented, taking into account patient age, tumor location (extra‐adrenal, intra‐adrenal, unilateral, and bilateral), biochemical presentation, and financial costs. This was based on cumulative frequencies ranging from 7.5% to 29% for germline mutations in four genes ( RET, VHL, SDHB, and SDHD) in patients with apparently sporadic pheochromocytomas. This algorithm will need to be validated by further genetic analysis, multicenter studies, and long‐term observations.