Clinical and molecular characteristics of the most common hereditary kidney cancer syndromes

Syndrome	Gene/protein	Chromosomal locus	Molecular pathway	Clinical features
Hereditary papillary renal cancer	c-MET	7q31	MET	Papillary RCC that is often multifocal and bilateral
Hereditary leiomyomatosis renal cell carcinoma	Fumarate hydratase	1q42	Krebs cycle/HIF1	Papillary RCC Cutaneous and uterine leiomyoma
Birt-Hogg-Dube	Folliculin	17p11	mTOR	Hybrid of oncocytic and chromophobe RCC; classic chromophobe, oncocytomas, and papillary RCC Fibrofolliculoma, pulmonary cysts, pneumothorax
Hereditary paraganglioma and pheochromocytoma	Succinate dehydrogenase	5p15	Krebs cycle/hypoxia	Clear cell, papillary, chromophobe, eosinophilic RCC Gastrointestinal stromal tumors, pheochromocytoma, paragangliomas
Tuberous sclerosis complex (TSC)	TSC1 TSC2	9q34 16p13	mTOR	Clear cell papillary, and chromophobe RCC; RCC with eosinophilic/oncocytic features Angiomyolipoma
von Hippel-Lindau (VHL)	VHL gene	3p25	HIF-1, HIF-2	Clear cell RCC Hemangioblastomas Retinal angiomas Pheochromocytoma Endolymphatic sac tumors of the middle ear Pancreatic tumors

RCC: renal cell carcinoma; HIF-1: hypoxia-inducible factor 1; HIF-2: hypoxia-inducible factor 2; mTOR: mammalian target of rapamycin.

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