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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.
Fuente: Nat Genet. 2014 Mar;46(3):225-33
Año de publicación: 2014
Nº de páginas: 24
Tipo de publicación: Artículo de Revista
DOI: 10.1038/ng.2891
ISSN: 1061-4036,1546-1718
Consultar en UCrea Leer publicación
GERLINGER, MARCO
HORSWELL, STUART
LARKIN, JAMES
ROWAN, ANDREW J
SALM, MAX P
IGNACIO VARELA EGOCHEAGA
FISHER, ROSALIE
MCGRANAHAN, NICHOLAS
MATTHEWS, NICHOLAS
SANTOS, CLAUDIO R
MARTÍNEZ, PIERRE
PHILLIMORE, BENJAMIN
BEGUM, SHARMIN
RABINOWITZ, ADAM
SPENCER-DENE, BRADLEY
GULATI, SAKSHI
BATES, PAUL A
STAMP, GORDON
PICKERING, LISA
GORE, MARTÍN
NICOL, DAVID L
HAZELL, STEVEN
FUTREAL, P ANDREW
STEWART, AENGUS
SWANTON, CHARLES
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