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 [2] National Research Centre 'Kurchatov Institute' 1 Akademika Kurchatova pl Moscow 123182 Russia

] Department of Human Genetics McGill University 1205 Dr Penfield Avenue Montreal Quebec Canada H3A 1B1 [2] Fondation Jean Dausset Centre d'Etude du Polymorphisme Humain 27 rue Juliette Dodu 75010 Paris France [3] Centre National de Génotypage CEA Institute de Génomique 2 rue Gaston Crémieux 91000 Evry France

] Department of Human Genetics McGill University 1205 Dr Penfield Avenue Montreal Quebec Canada H3A 1B1 [2] McGill University and Genome Quebec Innovation Centre 740 Doctor Penfield Avenue Montreal Quebec Canada H3A 0G1

1st Faculty of Medicine Institute of Hygiene and Epidemiology Charles University Prague Studničkova 7 Praha 2 128 00 Prague Czech Republic

Carol Davila University of Medicine and Pharmacy Th Burghele Hospital 20 Panduri Street 050659 Bucharest Romania

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

Centro Nacional de Análisis Genómico Baldiri Reixac 4 Barcleona Science Park Tower 1 08028 Barcelona Spain

Department of Cancer Epidemiology and Genetics Masaryk Memorial Cancer Institute and MF MU Zluty Kopec 7 656 53 Brno Czech Republic

Department of Pathology Karolinska Institutet SE 171 77 Stockholm Sweden

Department of Pathology The Beatson Institute for Cancer Research Switchback Road Bearsden Glasgow G61 1BD UK

European Molecular Biology Laboratory European Bioinformatics Institute EMBL EBI Wellcome Trust Genome Campus Hinxton CB10 1SD UK

Faculty of Medicine Institut National de la Santé et de la Recherche Medicale and University Toulouse 3 Paul Sabatier UMR 1027 37 allées Jules Guesde 31000 Toulouse France

Fondation Jean Dausset Centre d'Etude du Polymorphisme Humain 27 rue Juliette Dodu 75010 Paris France

Institute of Mathematics and Computer Science University of Latvia 29 Rainis Boulevard Riga LV 1459 Latvia

International Agency for Research on Cancer 150 cours Albert Thomas 69008 Lyon France

Leeds Institute of Cancer and Pathology University of Leeds Cancer Research Building St James's University Hospital Leeds LS9 7TF UK

Leeds Teaching Hospitals NHS Trust Pyrah Department of Urology Lincoln Wing St James's University Hospital Leeds LS9 7TF UK

McGill University and Genome Quebec Innovation Centre 740 Doctor Penfield Avenue Montreal Quebec Canada H3A 0G1

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

Citace poskytuje Crossref.org

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