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Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing

AuthorsGerlinger, Marco; Varela, Ignacio ; Swanton, Charles
Issue Date2014
PublisherNature Publishing Group
CitationNature Genetics 46(3): 225-233 (2014)
AbstractClear 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.
DescriptionPMCID: PMC4636053.-- et al.
Publisher version (URL)http://dx.doi.org/10.1038/ng.2891
Identifiersdoi: 10.1038/ng.2891
e-issn: 1546-1718
issn: 1061-4036
Appears in Collections:(IBBTEC) Artículos
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