| Entry |
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| Name |
Renal cell carcinoma
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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; Cancers
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| Pathway map |
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| Module |
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| Disease |
| Renal cell carcinoma | | von Hippel-Lindau syndrome |
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| Orthology |
| hypoxia-inducible factor 1 alpha | | hypoxia-inducible factor 2 alpha | | hypoxia-inducible factor prolyl hydroxylase [EC:1.14.11.-] | | von Hippel-Lindau disease tumor supressor | | transcription elongation factor B, polypeptide 1 | | transcription elongation factor B, polypeptide 2 | | RING-box protein 1 | | cullin 2 | | aryl hydrocarbon receptor nuclear translocator | | aryl hydrocarbon receptor nuclear translocator 2 | | | | MFS transporter, SP family, solute carrier family 2 (facilitated glucose transporter), member 1 | | vascular endothelial growth factor A | | transforming growth factor beta-1 | | transforming growth factor beta-2 | | transforming growth factor beta-3 | | transforming growth factor, alpha | | hepatocyte growth factor | | proto-oncogene tyrosine-protein kinase Met [EC: 2.7.10.1] | | GRB2-associated-binding protein 1 | | phosphatidylinositol-4,5-bisphosphate 3-kinase [EC: 2.7.1.153] | | phosphoinositide-3-kinase, regulatory subunit | | RAC serine/threonine-protein kinase [EC: 2.7.11.1] | | proto-oncogene C-crk | | Rap guanine nucleotide exchange factor (GEF) 1 | | Ras-related protein Rap-1A | | Ras-related protein Rap-1B | | tyrosine-protein phosphatase non-receptor type 11 [EC: 3.1.3.48] | | growth factor receptor-binding protein 2 | | son of sevenless | | GTPase HRas | | GTPase KRas | | GTPase NRas | | A-Raf proto-oncogene serine/threonine-protein kinase [EC: 2.7.11.1] | | B-Raf proto-oncogene serine/threonine-protein kinase [EC: 2.7.11.1] | | RAF proto-oncogene serine/threonine-protein kinase [EC: 2.7.11.1] | | mitogen-activated protein kinase kinase 1 [EC: 2.7.12.2] | | mitogen-activated protein kinase kinase 2 [EC: 2.7.12.2] | | extracellular signal-regulated kinase 1/2 [EC: 2.7.11.24] | | transcription factor AP-1 | | Ras-related C3 botulinum toxin substrate 1 | | cell division control protein 42 | | | | | | | | | | | | | | fumarate hydratase, class II [EC: 4.2.1.2] | | folliculin |
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| Compound |
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| Reference |
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| Authors |
Cohen HT, McGovern FJ. |
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| Title |
Renal-cell carcinoma. |
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| Journal |
N Engl J Med 353:2477-90 (2005) |
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| Reference |
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| Authors |
Pavlovich CP, Schmidt LS. |
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| Title |
Searching for the hereditary causes of renal-cell carcinoma. |
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| Journal |
Nat Rev Cancer 4:381-93 (2004) |
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| Reference |
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| Authors |
Linehan WM, Walther MM, Zbar B. |
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| Title |
The genetic basis of cancer of the kidney. |
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| Journal |
J Urol 170:2163-72 (2003) |
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| Reference |
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| Authors |
Birchmeier C, Birchmeier W, Gherardi E, Vande Woude GF. |
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| Title |
Met, metastasis, motility and more. |
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| Journal |
Nat Rev Mol Cell Biol 4:915-25 (2003) |
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| Reference |
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| Authors |
Kim WY, Kaelin WG. |
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| Title |
Role of VHL gene mutation in human cancer. |
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| Journal |
J Clin Oncol 22:4991-5004 (2004) |
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| Reference |
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| Authors |
Sudarshan S, Linehan WM, Neckers L. |
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| Title |
HIF and fumarate hydratase in renal cancer. |
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| Journal |
Br J Cancer 96:403-7 (2007) |
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| Reference |
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| Authors |
Sudarshan S, Pinto PA, Neckers L, Linehan WM. |
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| Title |
Mechanisms of disease: hereditary leiomyomatosis and renal cell cancer--a distinct form of hereditary kidney cancer. |
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| Journal |
Nat Clin Pract Urol 4:104-10 (2007) |
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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. |
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| Title |
Understanding familial and non-familial renal cell cancer. |
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| Journal |
Hum Mol Genet 11:2489-98 (2002) |
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