Entry 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.
Class Human Diseases; Cancer: specific typesBRITE hierarchy
Pathway map Disease Orthology K00922 PIK3CA_B_D; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha/beta/delta [EC:2.7.1.153 ]
K01679 E4.2.1.2B, fumC, FH; fumarate hydratase, class II [EC:4.2.1.2 ]
K02158 BAD; Bcl-2-antagonist of cell death
K02649 PIK3R1_2_3; phosphoinositide-3-kinase regulatory subunit alpha/beta/delta
K03871 VHL; von Hippel-Lindau disease tumor supressor
K04353 RAP1A; Ras-related protein Rap-1A
K04364 GRB2; growth factor receptor-bound protein 2
K04365 BRAF; B-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04366 RAF1; RAF proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K04368 MAP2K1, MEK1; mitogen-activated protein kinase kinase 1 [EC:2.7.12.2 ]
K04369 MAP2K2, MEK2; mitogen-activated protein kinase kinase 2 [EC:2.7.12.2 ]
K04392 RAC1; Ras-related C3 botulinum toxin substrate 1
K04393 CDC42; cell division control protein 42
K04438 CRK, CRKII; C-crk adapter molecule crk
K04448 JUN; transcription factor AP-1
K05099 MET, HGFR; proto-oncogene tyrosine-protein kinase Met [EC:2.7.10.1 ]
K05448 VEGFA; vascular endothelial growth factor A
K05460 HGF; hepatocyte growth factor
K06277 RAPGEF1, GRF2; Rap guanine nucleotide exchange factor 1
K06625 CDKN1A, P21, CIP1; cyclin-dependent kinase inhibitor 1A
K07293 PTPN11, SHP2; tyrosine-protein phosphatase non-receptor type 11 [EC:3.1.3.48 ]
K07299 SLC2A1, GLUT1; MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1
K07827 KRAS, KRAS2; GTPase KRas
K07836 RAP1B; Ras-related protein Rap-1B
K08268 HIF1A; hypoxia-inducible factor 1 alpha
K08774 TGFA; transforming growth factor, alpha
K08845 ARAF, ARAF1; A-Raf proto-oncogene serine/threonine-protein kinase [EC:2.7.11.1 ]
K09095 HIF2A, EPAS1; hypoxia-inducible factor 2 alpha
K09097 ARNT; aryl hydrocarbon receptor nuclear translocator
K09105 TFE3; transcription factor E3
K09593 GAB1; GRB2-associated-binding protein 1
K13105 PRCC; proline-rich protein PRCC
K13375 TGFB1; transforming growth factor beta-1
K13376 TGFB2; transforming growth factor beta-2
K13377 TGFB3; transforming growth factor beta-3
K15589 ARNT2; aryl hydrocarbon receptor nuclear translocator 2
K17386 PDGFB; platelet-derived growth factor subunit B
Compound Reference Authors Cohen HT, McGovern FJ.
Title Renal-cell carcinoma.
Journal Reference Authors Pavlovich CP, Schmidt LS.
Title Searching for the hereditary causes of renal-cell carcinoma.
Journal Reference Authors Linehan WM, Walther MM, Zbar B.
Title The genetic basis of cancer of the kidney.
Journal Reference Authors Kim WY, Kaelin WG.
Title Role of VHL gene mutation in human cancer.
Journal Reference Authors Sudarshan S, Linehan WM, Neckers L.
Title HIF and fumarate hydratase in renal cancer.
Journal Reference Authors Sudarshan S, Pinto PA, Neckers L, Linehan WM.
Title Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer.
Journal Reference Authors Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF.
Title Met, metastasis, motility and more.
Journal Reference Authors Muller-Hocker J, Babaryka G, Schmid I, Jung A
Title Overexpression of cyclin D1, D3, and p21 in an infantile renal carcinoma with Xp11.2 TFE3-gene fusion.
Journal Reference Authors Bodmer D, van den Hurk W, van Groningen JJ, Eleveld MJ, Martens GJ, Weterman MA, van Kessel AG.
Title Understanding familial and non-familial renal cell cancer.
Journal Reference Authors Kauffman EC, Ricketts CJ, Rais-Bahrami S, Yang Y, Merino MJ, Bottaro DP, Srinivasan R, Linehan WM
Title Molecular genetics and cellular features of TFE3 and TFEB fusion kidney cancers.
Journal Reference Authors Skalsky YM, Ajuh PM, Parker C, Lamond AI, Goodwin G, Cooper CS
Title PRCC, the commonest TFE3 fusion partner in papillary renal carcinoma is associated with pre-mRNA splicing factors.
Journal Reference Authors Medendorp K, van Groningen JJ, Vreede L, Hetterschijt L, Brugmans L, van den Hurk WH, van Kessel AG
Title The renal cell carcinoma-associated oncogenic fusion protein PRCCTFE3 provokes p21 WAF1/CIP1-mediated cell cycle delay.
Journal Related ko04120 Ubiquitin mediated proteolysis
