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Nat Commun. 2014 Oct 29;5:5135. doi: 10.1038/ncomms6135.

Variation in genomic landscape of clear cell renal cell carcinoma across Europe.

Author information

1
International Agency for Research on Cancer (IARC), 150 cours Albert Thomas, 69008 Lyon, France.
2
1] 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.
3
European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus, Hinxton CB10 1SD, UK.
4
McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, Quebec, Canada H3A 0G1.
5
Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James's University Hospital, Leeds LS9 7TF, UK.
6
Department of Pathology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
7
Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain, 27 rue Juliette Dodu, 75010 Paris, France.
8
Institute of Mathematics and Computer Science, University of Latvia, 29 Rainis Boulevard, Riga LV-1459, Latvia.
9
Department of Pathology, The Beatson Institute for Cancer Research, Switchback Road, Bearsden, Glasgow G61 1BD, UK.
10
Leeds Teaching Hospitals NHS Trust, Pyrah Department of Urology, Lincoln Wing, St James's University Hospital, Leeds LS9 7TF, UK.
11
First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague, Studničkova 7, Praha 2, 128 00 Prague, Czech Republic.
12
University Hospital Motol, V Úvalu 84, 150 06 Prague, Czech Republic.
13
Russian N.N. Blokhin Cancer Research Centre, Kashirskoye shosse 24, Moscow 115478, Russian Federation.
14
Department of Cancer Epidemiology and Genetics, Masaryk Memorial Cancer Institute and MF MU, Zluty Kopec 7, 656 53 Brno, Czech Republic.
15
National Institute of Public Health, Dr Leonte Anastasievici 1-3, sector 5, Bucuresti 050463, Romania.
16
Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital, 20 Panduri Street, 050659 Bucharest, Romania.
17
Centre 'Bioengineering', The Russian Academy of Sciences, Moscow 117312, Russian Federation.
18
National Research Centre 'Kurchatov Institute', 1 Akademika Kurchatova pl., Moscow 123182, Russia.
19
Centro Nacional de Análisis Genómico, Baldiri Reixac, 4, Barcleona Science Park - Tower I, 08028 Barcelona, Spain.
20
Centre National de Génotypage, CEA - Institute de Génomique, 2 rue Gaston Crémieux, 91000 Evry, France.
21
1] Centre 'Bioengineering', The Russian Academy of Sciences, Moscow 117312, Russian Federation [2] National Research Centre 'Kurchatov Institute', 1 Akademika Kurchatova pl., Moscow 123182, Russia.
22
Faculty of Medicine, Institut National de la Santé et de la Recherche Medicale (INSERM) and University Toulouse III-Paul Sabatier, UMR 1027, 37 allées Jules Guesde, 31000 Toulouse, France.
23
1] 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.

Abstract

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.

PMID:
25351205
DOI:
10.1038/ncomms6135
[Indexed for MEDLINE]

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