| Literature DB >> 24487277 |
Marco Gerlinger1, Stuart Horswell2, James Larkin3, Andrew J Rowan1, Max P Salm2, Ignacio Varela4, Rosalie Fisher3, Nicholas McGranahan1, Nicholas Matthews5, Claudio R Santos1, Pierre Martinez1, Benjamin Phillimore5, Sharmin Begum5, Adam Rabinowitz5, Bradley Spencer-Dene6, Sakshi Gulati7, Paul A Bates7, Gordon Stamp6, Lisa Pickering3, Martin Gore3, David L Nicol8, Steven Hazell9, P Andrew Futreal10, Aengus Stewart2, Charles Swanton1,11.
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.Entities:
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Year: 2014 PMID： 24487277 PMCID： PMC4636053 DOI： 10.1038/ng.2891
Source DB: PubMed Journal: Nat Genet ISSN： 1061-4036 Impact factor: 38.330