title: The molecular biology of renal cell carcinoma.
abstract: Renal cell carcinoma (RCC) includes a variety of disparate diseases, each of which displays interesting and novel molecular features, challenging some of the central tenets of cancer biology and lending unique insights into cancer-promoting mechanisms. The prevailing literature has focused on the most common type, the clear cell renal cell carcinoma (ccRCC) subgroup, in which familial and sporadic disease demonstrate similar molecular profiles. ccRCC is dominated by inactivating mutations in VHL, leading to constitutive activation of the hypoxia-inducible factors (HIFs) and resultant hypoxia response transcription signature, including changes that markedly affect cellular metabolic programs. Recent studies in ccRCC also have implicated mutations in regulators of chromatin remodeling and histone methylation. Although papillary and chromophobe histologies of RCC are highly distinct genetically, both have disruptions in metabolic signaling, suggesting that modulations of basic bioenergetics pathways may regulate kidney cell fates and phenotypes. Finally, emerging evidence of tumor heterogeneity and convergent evolution is reshaping our understanding of how these tumors evolve, underscoring which genetic events are driver mutations, and prompting further consideration of how to interpret molecular analyses of primary tumors in making assessments related to metastatic disease. The past few years have been a period of rapid discovery, which have expanded the opportunities for the renal cancer field to leverage new knowledge into developing diagnostic and therapeutic strategies.
authors: Department of Medicine, Division of Hematology/Oncology, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA, USA. Stephen.keefe@uphs.upenn.edu
authors: Stephen M
authors: SM
authors: Keefe
authors: Katherine L
authors: KL
authors: Nathanson
authors: W Kimryn
authors: WK
authors: Rathmell
mesh_terms: D051792:Basic Helix-Loop-Helix Proteins / Q000235:genetics; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D044127:Epigenesis, Genetic; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D058570:TOR Serine-Threonine Kinases / Q000502:physiology; D025521:Tumor Suppressor Proteins / Q000235:genetics; D043222:Ubiquitin Thiolesterase / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics; D000099162:Endothelial PAS Domain-Containing Protein 1
chemical_list: D051792:Basic Helix-Loop-Helix Proteins; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D058570:TOR Serine-Threonine Kinases; D025521:Tumor Suppressor Proteins; D043222:Ubiquitin Thiolesterase; D051794:Von Hippel-Lindau Tumor Suppressor Protein; D000099162:Endothelial PAS Domain-Containing Protein 1; C400134:BAP1 protein, human; C497442:HIF1A protein, human; C546842:MTOR protein, human; C497446:VHL protein, human