Renal cell cancer (RCC) accounts for ~3% of human malignancies and its incidence appears to be rising. Although most cases of RCC seem to occur sporadically, an inherited predisposition to renal cancer accounts for 1-4% of cases. RCC is not a single disease, it has several morphological subtypes. Conventional RCC (clear cell RCC) accounts for ~80% of cases, followed by papillary RCC (10-15%), chromophobe RCC (5%), and collecting duct RCC (<1%). Genes potentially involved in sporadic neoplasms of each particular type are VHL, MET, BHD, and FH respectively. In the absence of VHL, hypoxia-inducible factor alpha (HIF-alpha) accumulates, leading to production of several growth factors, including vascular endothelial growth factor and platelet-derived growth factor. Activated MET mediates a number of biological effects including motility, invasion of extracellular matrix, cellular transformation, prevention of apoptosis and metastasis formation. Loss of functional FH leads to accumulation of fumarate in the cell, triggering inhibition of HPH and preventing targeted pVHL-mediated degradation of HIF-alpha. BHD mutations cause the Birt-Hogg-Dube syndrome and its associated chromophobe, hybrid oncocytic, and conventional (clear cell) RCC.

Human Diseases; Cancer: specific types

nt06210  ERK signaling
nt06214  PI3K signaling
nt06225  HIF-1 signaling
nt06263  Hepatocellular carcinoma
nt06264  Renal cell carcinoma

Homo sapiens (human) [GN:hsa]

PMID:16339096

Cohen HT, McGovern FJ.

Renal-cell carcinoma.

N Engl J Med 353:2477-90 (2005)
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Searching for the hereditary causes of renal-cell carcinoma.

Nat Rev Cancer 4:381-93 (2004)
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Nat Rev Urol 11:465-75 (2014)
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