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  • As an entry-level screen for interacting signals, we generated global expression signatures of 76 hereditary and sporadic primary pheochromocytomas and paragangliomas. We show here that pheochromocytomas with VHL and SDHB or SDHD mutations form a tight cluster with a clear hypoxia and reduced oxidoreductase signature. This observation led to the identification of suppressed SDHB protein in tumors with VHL mutation and to the genetic demonstration that this effect is HIF-dependent. Our findings link pheochromocytomas with mutations in distinct genes—VHL, SDHB, and SDHD—and suggest that mitochondrial complex II inhibition contributes to development of pheochromocytomas with VHL mutation.


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