Entry |
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Name |
Renal cell carcinoma - Homo sapiens (human)
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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.
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Class |
Human Diseases; Cancer: specific types
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Pathway map |

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Network |
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Element |
N00005 | Mutation-activated MET to RAS-ERK signaling pathway |
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 |
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Disease |
H00559 | von Hippel-Lindau syndrome |
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Drug |
D06272 | Sorafenib tosylate (USAN) |
D10095 | Cabozantinib s-malate (USAN) |
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Organism |
Homo sapiens (human) [GN: hsa]
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Gene |
3091 | HIF1A; hypoxia inducible factor 1 subunit alpha [KO:K08268] |
2034 | EPAS1; endothelial PAS domain protein 1 [KO:K09095] |
7428 | VHL; von Hippel-Lindau tumor suppressor [KO:K03871] |
405 | ARNT; aryl hydrocarbon receptor nuclear translocator [KO:K09097] |
9915 | ARNT2; aryl hydrocarbon receptor nuclear translocator 2 [KO:K15589] |
6513 | SLC2A1; solute carrier family 2 member 1 [KO:K07299] |
7422 | VEGFA; vascular endothelial growth factor A [KO:K05448] |
7040 | TGFB1; transforming growth factor beta 1 [KO:K13375] |
7042 | TGFB2; transforming growth factor beta 2 [KO:K13376] |
7043 | TGFB3; transforming growth factor beta 3 [KO:K13377] |
5155 | PDGFB; platelet derived growth factor subunit B [KO:K17386] |
7039 | TGFA; transforming growth factor alpha [KO:K08774] |
2549 | GAB1; GRB2 associated binding protein 1 [KO:K09593] |
5290 | PIK3CA; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha [KO:K00922] [EC:2.7.1.153] |
5293 | PIK3CD; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit delta [KO:K00922] [EC:2.7.1.153] |
5291 | PIK3CB; phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta [KO:K00922] [EC:2.7.1.153] |
5295 | PIK3R1; phosphoinositide-3-kinase regulatory subunit 1 [KO:K02649] |
5296 | PIK3R2; phosphoinositide-3-kinase regulatory subunit 2 [KO:K02649] |
8503 | PIK3R3; phosphoinositide-3-kinase regulatory subunit 3 [KO:K02649] |
572 | BAD; BCL2 associated agonist of cell death [KO:K02158] |
1398 | CRK; CRK proto-oncogene, adaptor protein [KO:K04438] |
1399 | CRKL; CRK like proto-oncogene, adaptor protein [KO:K04438] |
2889 | RAPGEF1; Rap guanine nucleotide exchange factor 1 [KO:K06277] |
5906 | RAP1A; RAP1A, member of RAS oncogene family [KO:K04353] |
5908 | RAP1B; RAP1B, member of RAS oncogene family [KO:K07836] |
2885 | GRB2; growth factor receptor bound protein 2 [KO:K04364] |
6654 | SOS1; SOS Ras/Rac guanine nucleotide exchange factor 1 [KO:K03099] |
6655 | SOS2; SOS Ras/Rho guanine nucleotide exchange factor 2 [KO:K03099] |
3265 | HRAS; HRas proto-oncogene, GTPase [KO:K02833] |
3845 | KRAS; KRAS proto-oncogene, GTPase [KO:K07827] |
4893 | NRAS; NRAS proto-oncogene, GTPase [KO:K07828] |
2113 | ETS1; ETS proto-oncogene 1, transcription factor [KO:K02678] |
3725 | JUN; Jun proto-oncogene, AP-1 transcription factor subunit [KO:K04448] |
998 | CDC42; cell division cycle 42 [KO:K04393] |
5546 | PRCC; proline rich mitotic checkpoint control factor [KO:K13105] |
7030 | TFE3; transcription factor binding to IGHM enhancer 3 [KO:K09105] |
1026 | CDKN1A; cyclin dependent kinase inhibitor 1A [KO:K06625] |
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Compound |
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Reference |
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Authors |
Cohen HT, McGovern FJ. |
Title |
Renal-cell carcinoma. |
Journal |
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Reference |
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Authors |
Pavlovich CP, Schmidt LS. |
Title |
Searching for the hereditary causes of renal-cell carcinoma. |
Journal |
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Reference |
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Authors |
Linehan WM, Walther MM, Zbar B. |
Title |
The genetic basis of cancer of the kidney. |
Journal |
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Reference |
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Authors |
Kim WY, Kaelin WG. |
Title |
Role of VHL gene mutation in human cancer. |
Journal |
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Reference |
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Authors |
Sudarshan S, Linehan WM, Neckers L. |
Title |
HIF and fumarate hydratase in renal cancer. |
Journal |
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Reference |
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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 |
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Reference |
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Authors |
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. |
Title |
Met, metastasis, motility and more. |
Journal |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Reference |
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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 |
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Related pathway |
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KO pathway |
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LinkDB |
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