Variation in genomic landscape of clear cell renal cell carcinoma across Europe
Language English Country Great Britain, England Media electronic
Document type Journal Article, Research Support, Non-U.S. Gov't
Grant support
001
World Health Organization - International
MR/L01629X/1
Medical Research Council - United Kingdom
Cancer Research UK - United Kingdom
PubMed
25351205
DOI
10.1038/ncomms6135
PII: ncomms6135
Knihovny.cz E-resources
- MeSH
- Adult MeSH
- Focal Adhesions metabolism MeSH
- Phosphatidylinositol 3-Kinases genetics MeSH
- Oncogene Proteins, Fusion genetics MeSH
- Genetic Variation * MeSH
- Genome, Human genetics MeSH
- Genomics * MeSH
- Carcinoma, Renal Cell genetics MeSH
- Cohort Studies MeSH
- Middle Aged MeSH
- Humans MeSH
- Mutation MeSH
- Mutation Rate MeSH
- Gene Expression Regulation, Neoplastic MeSH
- Sequence Analysis, DNA MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- RNA Splicing genetics MeSH
- Signal Transduction genetics MeSH
- Gene Expression Profiling MeSH
- Check Tag
- Adult MeSH
- Middle Aged MeSH
- Humans MeSH
- Male MeSH
- Aged, 80 and over MeSH
- Aged MeSH
- Female MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
- Geographicals
- Europe MeSH
- Names of Substances
- Phosphatidylinositol 3-Kinases MeSH
- Oncogene Proteins, Fusion MeSH
The incidence of renal cell carcinoma (RCC) is increasing worldwide, and its prevalence is particularly high in some parts of Central Europe. Here we undertake whole-genome and transcriptome sequencing of clear cell RCC (ccRCC), the most common form of the disease, in patients from four different European countries with contrasting disease incidence to explore the underlying genomic architecture of RCC. Our findings support previous reports on frequent aberrations in the epigenetic machinery and PI3K/mTOR signalling, and uncover novel pathways and genes affected by recurrent mutations and abnormal transcriptome patterns including focal adhesion, components of extracellular matrix (ECM) and genes encoding FAT cadherins. Furthermore, a large majority of patients from Romania have an unexpected high frequency of A:T>T:A transversions, consistent with exposure to aristolochic acid (AA). These results show that the processes underlying ccRCC tumorigenesis may vary in different populations and suggest that AA may be an important ccRCC carcinogen in Romania, a finding with major public health implications.
Centre 'Bioengineering' The Russian Academy of Sciences Moscow 117312 Russian Federation
Centre National de Génotypage CEA Institute de Génomique 2 rue Gaston Crémieux 91000 Evry France
Department of Pathology Karolinska Institutet SE 171 77 Stockholm Sweden
International Agency for Research on Cancer 150 cours Albert Thomas 69008 Lyon France
National Institute of Public Health Dr Leonte Anastasievici 1 3 sector 5 Bucuresti 050463 Romania
National Research Centre 'Kurchatov Institute' 1 Akademika Kurchatova pl Moscow 123182 Russia
Russian N N Blokhin Cancer Research Centre Kashirskoye shosse 24 Moscow 115478 Russian Federation
University Hospital Motol 5 Úvalu 84 150 06 Prague Czech Republic
References provided by Crossref.org
Understanding the biological processes of kidney carcinogenesis: an integrative multi-omics approach
Geographic variation of mutagenic exposures in kidney cancer genomes
The Mutographs biorepository: A unique genomic resource to study cancer around the world
Genome-wide association study identifies multiple risk loci for renal cell carcinoma
Balkan endemic nephropathy: an update on its aetiology
International cancer seminars: a focus on kidney cancer
