H00021 | |
H number | H00021 |
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. |
Category | Cancer DIS_PATHWAY hsa05211 Renal cell carcinoma |
Network | nt06264 Renal cell carcinoma nt06504(H00021) Base excision repair |
Gene | PRCC-TFE3 (translocation) [HSA:5546 7030] [KO:K13105 K09105] 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] FLCN (germline mutation (Birt-Hogg-Dube syndrome)) [HSA:201163] [KO:K09594] HNF1A [HSA:6927] [KO:K08036] OGG1 [HSA:4968] [KO:K03660] PBRM1 [HSA:55193] [KO:K11757] |
Pathogen | - |
Env factor | - |
Carcinogen | - |
Drug | Medroxyprogesterone acetate [DR:D00951] Temsirolimus [DR:D06068] Everolimus [DR:D02714] Axitinib [DR:D03218] Tivozanib hydrochloride [DR:D10190] Sunitinib malate [DR:D06402] Sorafenib tosylate [DR:D06272] Pazopanib hydrochloride [DR:D05380] Cabozantinib s-malate [DR:D10095] Lenvatinib mesylate [DR:D09920] Nivolumab [DR:D10316] Pembrolizumab [DR:D10574] Avelumab [DR:D10817] Bevacizumab [DR:D06409] Ipilimumab [DR:D04603] (MSI-H or dMMR) Aldesleukin [DR:D00748] |
Comment | - |
Other DBs | ICD-11: 2C90.0 ICD-10: C64 MeSH: D002292 OMIM: 144700 300854 605074 |
Reference | PMID:15122209 (VHL, MET, FH, FLCN) AUTHORS Pavlovich CP, Schmidt LS. TITLE Searching for the hereditary causes of renal-cell carcinoma. JOURNAL Nat Rev Cancer 4:381-93 (2004) DOI:10.1038/nrc1364 PMID:16339096 AUTHORS Cohen HT, McGovern FJ. TITLE Renal-cell carcinoma. JOURNAL N Engl J Med 353:2477-90 (2005) DOI:10.1056/NEJMra043172 PMID:15380513 AUTHORS Linehan WM, Zbar B. TITLE Focus on kidney cancer. JOURNAL Cancer Cell 6:223-8 (2004) DOI:10.1016/j.ccr.2004.09.006 PMID:19406209 (PRCC-TFE3) AUTHORS Brenner JC, Chinnaiyan AM TITLE Translocations in epithelial cancers. JOURNAL Biochim Biophys Acta 1796:201-15 (2009) DOI:10.1016/j.bbcan.2009.04.005 PMID:19233641 AUTHORS Prensner JR, Chinnaiyan AM TITLE Oncogenic gene fusions in epithelial carcinomas. JOURNAL Curr Opin Genet Dev 19:82-91 (2009) DOI:10.1016/j.gde.2008.11.008 PMID:15649945 (HNF1A) AUTHORS Rebouissou S, Vasiliu V, Thomas C, Bellanne-Chantelot C, Bui H, Chretien Y, Timsit J, Rosty C, Laurent-Puig P, Chauveau D, Zucman-Rossi J TITLE Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas. JOURNAL Hum Mol Genet 14:603-14 (2005) DOI:10.1093/hmg/ddi057 PMID:10987279 (OGG1) AUTHORS Audebert M, Chevillard S, Levalois C, Gyapay G, Vieillefond A, Klijanienko J, Vielh P, El Naggar AK, Oudard S, Boiteux S, Radicella JP TITLE Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney. JOURNAL Cancer Res 60:4740-4 (2000) PMID:29301960 (PBRM1) AUTHORS Miao D, Margolis CA, Gao W, Voss MH, Li W, Martini DJ, Norton C, Bosse D, Wankowicz SM, Cullen D, Horak C, Wind-Rotolo M, Tracy A, Giannakis M, Hodi FS, Drake CG, Ball MW, Allaf ME, Snyder A, Hellmann MD, Ho T, Motzer RJ, Signoretti S, Kaelin WG Jr, Choueiri TK, Van Allen EM TITLE Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma. JOURNAL Science 359:801-806 (2018) DOI:10.1126/science.aan5951 |