Succinate dehydrogenase in cancer

Inherited forms of pheochromocytomas, paragangliomas (PPGL), stromal gastro-intestinal tumors (GIST) and rare forms of renal cancers can be caused by mutations in genes encoding the 4 subunits of the mitochondrial enzyme succinate dehydrogenase (SDH), involved in the tricarboxylic acid (TCA) cycle and the electron transport chain. While mutations in SDHA, SDHC and SDHD genes cause benign tumors, loss-of-function mutations in the SDHB subunit predispose to metastatic tumors characterized by pseudohypoxic and hypermethylator phenotypes. In this presentation, I will give an overview of the recent studies performed in our lab on both tumor samples and experimental models, to decipher the molecular, metabolic and epigenetic responses that lead to this aggressive behavior.