Pheochromocytoma and paraganglioma susceptibility genes: Estimating the associated risk of disease
Menée à partir de données européennes, américaines et asiatiques, cette étude prospective met en évidence le rôle de mutations constitutionnelles des gènes SDHA, TMEM127, MAX et SDHAF2 dans l'étiologie du phéochromocytome et du paragangliome
Approximately 40% of the tumors of the autonomic nervous system, pheochromocytomas and paragangliomas (PCC/PGL), are associated with an underlying inherited mutation, more than any other tumor type. Thus, germline mutation testing is recommended for all patients with PCC/PGL. Strong evidence supports an association of susceptibility for PCC/PGL with germline mutations in 10 genes (FH, MAX, NF1, RET, SDHA, SDHB, SDHC, SDHD, TMEM127, and VHL); mutations in an additional 5 genes also have been associated with disease susceptibility but with lower levels of evidence (EGLN1 [PHD2], EPAS1 [HIF2A], KIF1B, MET, and SDHAF2).1 Even for genes in which an association between mutation and disease has been well established, the frequency of mutations is quite rare; thus, a paucity of data exist on which to base clinical recommendations for patients regarding the risk for developing the first PCC/PGL (eg, if they are identified though familial mutation testing), additional primary PCC/PGLs, metastatic disease, and other tumor types.
JAMA Oncology , commentaire, 2016