Recently, clinical and fundamental research studies have dramatically changed the knowledge on the genetics of pheochromocytoma (PH). Previously, it was widely accepted that only 10% of the patients affected by a PH had a familial disease and that the malignant phenotype of a PH could not be diagnosed before the occurrence of the first metastasis. After the identification of the genes involved in the hereditary paraganglioma/pheochromocytoma syndrome (SDHD, SDHB, SDHC)13, it has been demonstrated that 25% to 30% of the patients have a hereditary PH due to a germline mutation on SDHB, SDHD, VHL, RET or NF1 genes34 and that the identification of a SDHB mutation is a high risk factor for malignancy and poor prognosis46. Those data have supported new recommendations for genetic counselling and genetic testing as well as for the management of the affected patients79. Moreover, fundamental research studies have contributed to the understanding of new molecular mechanisms involved in the PH tumorigenesis. In particular, it has been shown that SDHs genes are new mitochondrial tumour suppressive genes and that the succinate dehydrogenase inactivation induces an abnormal stimulation of the hypoxia-angiogenesis pathway1011.
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03 - 07 May 2008
European Society of Endocrinology