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  • Adrenal and extra-adrenal pheochromocytomas (also known as paragangliomas) are catecholamine-secreting tumors derived from chromaffin cells of neural crest origin [[pgen-0010008-b01]]. Pheochromocytomas can arise as a result of mutations in the following disease-associated genes: RET in multiple endocrine neoplasia type 2 (MEN2); VHL in von Hippel-Lindau disease (VHL); NF1 in neurofibromatosis type 1 (NF1); and succinate dehydrogenase (SDH) subunits B, C, or D in familial paraganglioma syndromes type 4 (PGL4), type 3 (PGL3), and type 1 (PGL1), respectively [[pgen-0010008-b02]]. The various pheochromocytoma susceptibility genes modulate a variety of signaling pathways that are superficially unrelated to one another. However, the uniform phenotype of the tumors that arise from these distinct genetic lesions suggests the presence of underlying biochemical links.

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