|Name||Renal cell carcinoma|
|Description||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.|
N00044 Mutation-activated MET to PI3K signaling pathway
N00080 Loss of VHL to HIF-1 signaling pathway
N00081 Mutation-inactivated VHL to HIF-1 signaling pathway
N00127 PRCC-TFE3 fusion to transcriptional activation
|Gene||VHL (germline mutation (VHL disease), somatic mutation) [HSA:7428] [KO:K03871]
Met (germline activating mutation (HPRC), somatic activating mutation) [HSA:4233] [KO:K05099]
FH (germline loss-of-function mutation (HLPCC), LOH, somatic mutation) [HSA:2271] [KO:K01679]
BHD (germline mutation (Birt-Hogg-Dube syndrome)) [HSA:201163] [KO:K09594]
PRCC-TFE3 (translocation) [HSA:5546 7030] [KO:K13105 K09105]
Cadmium and cadmium compounds
Radium-224 and its decay products
Tobacco smoking and tobacco smoke
VEGF [HSA:7422 7423 7424 2277]
|Comment||ICD-O: 8310/3, Tumor type: Clear cell carcinoma
ICD-O: 8260/3, Tumor type: Papillary renal cell carcinoma
ICD-O: 8317/3, Tumor type: Chromophobe renal cell carcinoma
ICD-O: 8290/0, Tumor type: Oncocytoma
ICD-O: 8319/3, Tumor type: Carcinoma of the collecting ducts of Bellini
|Other DBs||ICD-10: C64
|Reference||PMID:15122209 (gene, tumor type)
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