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Genomic architecture and evolution of clear cell renal cell carcinomas defined by multiregion sequencing
- Source :
- Nat Genet. 2014 Mar;46(3):225-33, Digital.CSIC. Repositorio Institucional del CSIC, instname, UCrea Repositorio Abierto de la Universidad de Cantabria, Universidad de Cantabria (UC)
- Publication Year :
- 2014
-
Abstract
- PMCID: PMC4636053.-- et al.<br />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.<br />C.S. and M. Gerlinger are supported by grants from Cancer Research UK Biomarkers and Imaging Discovery and Development Committee (BIDD), the Medical Research Council and the Seventh European Union Framework Programme, and C.S. is supported by the Breast Cancer Research Foundation and the Rosetrees Trust. We acknowledge the Ramón y Cajal program of the Ministerio de Economía y Competitividad, Spain, and Novartis for funding support for E-PREDICT clinical trials. This study was supported by researchers at the National Institute for Health Research Biomedical Research Centres at University College London Hospitals and at the Royal Marsden Hospital.
- Subjects :
- DNA Copy Number Variations
Class I Phosphatidylinositol 3-Kinases
Genomics
Biology
Polymorphism, Single Nucleotide
PBRM1
Evolution, Molecular
Phosphatidylinositol 3-Kinases
03 medical and health sciences
0302 clinical medicine
Renal cell carcinoma
Genetics
medicine
Humans
Exome
Carcinoma, Renal Cell
Phylogeny
Exome sequencing
030304 developmental biology
0303 health sciences
Tumor Suppressor Proteins
High-Throughput Nucleotide Sequencing
Nuclear Proteins
Histone-Lysine N-Methyltransferase
medicine.disease
Kidney Neoplasms
3. Good health
DNA-Binding Proteins
CpG site
Von Hippel-Lindau Tumor Suppressor Protein
Tumor progression
030220 oncology & carcinogenesis
Mutation
Disease Progression
Cancer research
CpG Islands
Ubiquitin Thiolesterase
Clear cell
Transcription Factors
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Nat Genet. 2014 Mar;46(3):225-33, Digital.CSIC. Repositorio Institucional del CSIC, instname, UCrea Repositorio Abierto de la Universidad de Cantabria, Universidad de Cantabria (UC)
- Accession number :
- edsair.doi.dedup.....110536728214a41f21714ee7957f7b6f