Fig. 1.

Hereditary kidney cancer. Kidney cancer is not a single entity but made up of a number of different types of cancer, each with a distinct histology, caused by a different gene, with a different clinical course, and responding differently to therapy. Germline von Hippel-Lindau (VHL) gene mutations cause von Hippel-Lindau disease and clear cell kidney tumors. Germline MET oncogene mutations predispose to hereditary papillary renal carcinoma with type 1 papillary tumors. Germline mutations in the folliculin (FLCN) gene are inherited in patients with Birt-Hogg-Dubé syndrome who present with hybrid oncocytic tumors, chromophobe renal tumors and benign oncocytomas. Germline fumarate hydratase (FH) gene mutations in patients with hereditary leiomyomatosis and renal cell carcinoma predispose affected individuals to develop renal tumors with papillary type 2 histology. Germline mutations in the genes encoding subunits of succinate dehydrogenase, SDHB/SDHC/SDHD, predispose to renal tumors with an oncocytic phenotype in SDH-deficient RCC patients. Patients with tuberous sclerosis complex inherit germline mutations in tuberous sclerosis complex 1 or 2 (TSC1, TSC2) genes and are at risk to develop angiomyolipomas in the kidney and, occasionally, renal tumors. Adapted and reprinted with permission [97].