title: Genetic basis of kidney cancer: role of genomics for the development of disease-based therapeutics.
abstract: Kidney cancer is not a single disease; it is made up of a number of different types of cancer, including clear cell, type 1 papillary, type 2 papillary, chromophobe, TFE3, TFEB, and oncocytoma. Sporadic, nonfamilial kidney cancer includes clear cell kidney cancer (75%), type 1 papillary kidney cancer (10%), papillary type 2 kidney cancer (including collecting duct and medullary RCC) (5%), the microphalmia-associated transcription (MiT) family translocation kidney cancers (TFE3, TFEB, and MITF), chromophobe kidney cancer (5%), and oncocytoma (5%). Each has a distinct histology, a different clinical course, responds differently to therapy, and is caused by mutation in a different gene. Genomic studies identifying the genes for kidney cancer, including the VHL, MET, FLCN, fumarate hydratase, succinate dehydrogenase, TSC1, TSC2, and TFE3 genes, have significantly altered the ways in which patients with kidney cancer are managed. While seven FDA-approved agents that target the VHL pathway have been approved for the treatment of patients with advanced kidney cancer, further genomic studies, such as whole genome sequencing, gene expression patterns, and gene copy number, will be required to gain a complete understanding of the genetic basis of kidney cancer and of the kidney cancer gene pathways and, most importantly, to provide the foundation for the development of effective forms of therapy for patients with this disease.
authors.affiliation: Urologic Oncology Branch, National Cancer Institute, Bethesda, MD 20892, USA. linehanm@mail.nih.gov
authors.forename: W Marston
authors.initials: WM
authors.lastname: Linehan
mesh_terms: D000970:Antineoplastic Agents; D002277:Carcinoma / Q000188:drug therapy / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D052138:Genes, Neoplasm; D020022:Genetic Predisposition to Disease; D023281:Genomics; D006801:Humans; D007680:Kidney Neoplasms / Q000188:drug therapy / Q000235:genetics*; D009154:Mutation
chemical_list: D000970:Antineoplastic Agents