@article {569411,
	title = {Comprehensive molecular characterization of clear cell renal cell carcinoma.},
	journal = {Nature},
	volume = {499},
	number = {7456},
	year = {2013},
	month = {2013 Jul 4},
	pages = {43-9},
	abstract = {Genetic changes underlying clear cell renal cell carcinoma (ccRCC) include alterations in genes controlling cellular oxygen sensing (for example, VHL) and the maintenance of chromatin states (for example, PBRM1). We surveyed more than 400 tumours using different genomic platforms and identified 19 significantly mutated genes. The PI(3)K/AKT pathway was recurrently mutated, suggesting this pathway as a potential therapeutic target. Widespread DNA hypomethylation was associated with mutation of the H3K36 methyltransferase SETD2, and integrative analysis suggested that mutations involving the SWI/SNF chromatin remodelling complex (PBRM1, ARID1A, SMARCA4) could have far-reaching effects on other pathways. Aggressive cancers demonstrated evidence of a metabolic shift, involving downregulation of genes involved in the TCA cycle, decreased AMPK and PTEN protein levels, upregulation of the pentose phosphate pathway and the glutamine transporter genes, increased acetyl-CoA carboxylase protein, and altered promoter methylation of miR-21 (also known as MIR21) and GRB10. Remodelling cellular metabolism thus constitutes a recurrent pattern in ccRCC that correlates with tumour stage and severity and offers new views on the opportunities for disease treatment.},
	keywords = {Acetyl-CoA Carboxylase, AMP-Activated Protein Kinases, Carcinoma, Renal Cell, Chromatin, Chromatin Assembly and Disassembly, Citric Acid Cycle, DNA Methylation, DNA Mutational Analysis, Epigenesis, Genetic, Gene Expression Profiling, Gene Expression Regulation, Neoplastic, Genome, Human, Genomics, GRB10 Adaptor Protein, Histone-Lysine N-Methyltransferase, Humans, Metabolic Networks and Pathways, MicroRNAs, Mutation, Pentose Phosphate Pathway, Phosphatidylinositol 3-Kinases, Proto-Oncogene Proteins c-akt, PTEN Phosphohydrolase, RNA, Neoplasm, Signal Transduction, Survival Analysis},
	issn = {1476-4687},
	doi = {10.1038/nature12222},
	author = {Cancer Genome Atlas Network, The Cancer Genome Atlas}
}
