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, repair and transcription
nt06504 Base excision repair
H00021 Renal cell carcinoma
Signal transduction
nt06542 HIF signaling
H00021 Renal cell carcinoma
Cancer-associated carbohydrates [br08441.html]
H00021
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.
von Hippel-Lindau syndrome is an autosomal dominant disorder associated with tumors in the central nervous system and other organs. The most frequent tumors are cerebellar and retinal haemangioblastomas, pancreatic neuroendocrine tumors, renal cell carcinoma, phaeochromocytoma in the adrenal gland, epididymal cystadenoma, and endolymphatic sac tumors. Germline inactivation of VHL tumor suppressor protein leads to the upregulation of HIF and promotes to carcinogenesis.
Category
Congenital malformation
Brite
Human diseases in ICD-11 classification [BR:br08403]
20 Developmental anomalies
Multiple developmental anomalies or syndromes
LD2D Phakomatoses or hamartoneoplastic syndromes
H00559 von Hippel-Lindau syndrome
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06542 HIF signaling
H00559 von Hippel-Lindau syndrome
Zatyka M, da Silva NF, Clifford SC, Morris MR, Wiesener MS, Eckardt KU, Houlston RS, Richards FM, Latif F, Maher ER
Title
Identification of cyclin D1 and other novel targets for the von Hippel-Lindau tumor suppressor gene by expression array analysis and investigation of cyclin D1 genotype as a modifier in von Hippel-Lindau disease.
Congenital polycythemia or familial erythrocytosis includes a heterogeneous group of disorders with the common characteristic of an absolute increased red cell mass caused by inherited defects in hypoxia sensing. In primary polycythemias there is an innate defect in the hematopoietic progenitors which allows constitutive overproduction whereas in secondary polycythemias normal progenitors are acted on by serum erythropoietin.
Category
Hematologic disease
Brite
Human diseases in ICD-11 classification [BR:br08403]
03 Diseases of the blood or blood-forming organs
Anaemias or other erythrocyte disorders
Polycythaemia
3A80 Congenital polycythaemia
H00236 Congenital polycythemia
Pathway-based classification of diseases [BR:br08402]
Signal transduction
nt06518 JAK-STAT signaling
H00236 Congenital polycythemia
nt06542 HIF signaling
H00236 Congenital polycythemia
Cellular processes
nt06535 Efferocytosis
H00236 Congenital polycythemia
