A Comprehensive Next Generation Sequencing–Based Genetic Testing Strategy To Improve Diagnosis of Inherited Pheochromocytoma and Paraganglioma

Context: Pheochromocytomas and paragangliomas are notable for a high frequency of inherited cases, many of which present as apparently sporadic tumors. Objective: The objective of this study was to establish a comprehensive next generation sequencing (NGS)–based strategy for the diagnosis of patients with pheochromocytoma and paraganglioma by testing simultaneously for mutations in MAX, RET, SDHA, SDHB, SDHC, SDHD, SDHAF2, TMEM127, and VHL. Design: After the methodology for the assay was designed and established, it was validated on DNA samples with known genotype and then patients were studied prospectively. Setting: The study was performed in a diagnostic genetics laboratory. Patients: DNA samples from 205 individuals affected with adrenal or extraadrenal pheochromocytoma/head and neck paraganglioma (PPGL/HNPGL) were analyzed. A proof-of-principle study was performed using 85 samples known to contain a variant in 1 or more of the genes to be tested, followed by prospective analysis of an additional 120 ...