@article{10902/9690, year = {2014}, url = {http://hdl.handle.net/10902/9690}, abstract = {Clear cell renal carcinomas (ccRCCs) can display intratumor heterogeneity (ITH). We applied multiregion exome sequencing (M-seq) to resolve the genetic architecture and evolutionary histories of ten ccRCCs. Ultra-deep sequencing identified ITH in all cases. We found that 73–75% of identified ccRCC driver aberrations were subclonal, confounding estimates of driver mutation prevalence. ITH increased with the number of biopsies analyzed, without evidence of saturation in most tumors. Chromosome 3p loss and VHL aberrations were the only ubiquitous events. The proportion of C>T transitions at CpG sites increased during tumor progression. M-seq permits the temporal resolution of ccRCC evolution and refines mutational signatures occurring during tumor development.}, publisher = {Nat Genet. 2014 Mar;46(3):225-33}, title = {Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing}, author = {Gerlinger, Marco and Horswell, Stuart and Larkin, James and Rowan, Andrew J and Salm, Max P and Varela Egocheaga, Ignacio and Fisher, Rosalie and McGranahan, Nicholas and Matthews, Nicholas and Santos, Claudio R and Martínez, Pierre and Phillimore, Benjamin and Begum, Sharmin and Rabinowitz, Adam and Spencer-Dene, Bradley and Gulati, Sakshi and Bates, Paul A and Stamp, Gordon and Pickering, Lisa and Gore, Martín and Nicol, David L and Hazell, Steven and Futreal, P Andrew and Stewart, Aengus and Swanton, Charles}, }