KEGG   DISEASE: Renal cell carcinoma
H00021                      Disease                                
Renal cell carcinoma
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.
Human diseases in ICD-11 classification [BR:br08403]
 02 Neoplasms
  Malignant neoplasms, except primary neoplasms of lymphoid, haematopoietic, central nervous system or related tissues
   Malignant neoplasms, stated or presumed to be primary, of specified sites, except of lymphoid, haematopoietic, central nervous system or related tissues
    Malignant neoplasms of urinary tract
     2C90  Malignant neoplasms of kidney, except renal pelvis
      H00021  Renal cell carcinoma
Pathway-based classification of diseases [BR:br08402]
 Replication and repair
  nt06504  Base excision repair
   H00021  Renal cell carcinoma
Cancer-associated carbohydrates [br08441.html]
hsa05211  Renal cell carcinoma
nt06264 Renal cell carcinoma
nt06504 Base excision repair
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]
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]
Other DBs
ICD-11: 2C90.0
ICD-10: C64
MeSH: D002292
OMIM: 144700 300854 605074
PMID:15122209 (VHL, MET, FH, FLCN)
Pavlovich CP, Schmidt LS.
Searching for the hereditary causes of renal-cell carcinoma.
Nat Rev Cancer 4:381-93 (2004)
Cohen HT, McGovern FJ.
Renal-cell carcinoma.
N Engl J Med 353:2477-90 (2005)
Linehan WM, Zbar B.
Focus on kidney cancer.
Cancer Cell 6:223-8 (2004)
PMID:19406209 (PRCC-TFE3)
Brenner JC, Chinnaiyan AM
Translocations in epithelial cancers.
Biochim Biophys Acta 1796:201-15 (2009)
Prensner JR, Chinnaiyan AM
Oncogenic gene fusions in epithelial carcinomas.
Curr Opin Genet Dev 19:82-91 (2009)
PMID:15649945 (HNF1A)
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
Germline hepatocyte nuclear factor 1alpha and 1beta mutations in renal cell carcinomas.
Hum Mol Genet 14:603-14 (2005)
PMID:10987279 (OGG1)
Audebert M, Chevillard S, Levalois C, Gyapay G, Vieillefond A, Klijanienko J, Vielh P, El Naggar AK, Oudard S, Boiteux S, Radicella JP
Alterations of the DNA repair gene OGG1 in human clear cell carcinomas of the kidney.
Cancer Res 60:4740-4 (2000)
PMID:29301960 (PBRM1)
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
Genomic correlates of response to immune checkpoint therapies in clear cell renal cell carcinoma.
Science 359:801-806 (2018)

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