KEGG DISEASE: Renal cell carcinoma

DISEASE: Renal cell carcinoma

Entry

H00021                      Disease

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

Brite

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]
H00021

Disease
pathway

hsa05211

Renal cell carcinoma

Network

nt06264 Renal cell carcinoma
nt06504 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]

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]

Other DBs

ICD-11:

ICD-10:

MeSH:

OMIM:

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

Reference

PMID:16339096

Authors

Cohen HT, McGovern FJ.

Title

Renal-cell carcinoma.

Journal

N Engl J Med 353:2477-90 (2005)
DOI:10.1056/NEJMra043172

Reference

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

Reference

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

Reference

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

Reference

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

Reference

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)

Reference

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

LinkDB

» Japanese version

DBGET integrated database retrieval system