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

Ghislaine Scelo, Yasser Riazalhosseini, Liliana Greger, Louis Letourneau, Mar Gonzàlez-Porta, Magdalena B. Wozniak, Mathieu Bourgey, Patricia Harnden, Lars Egevad, Sharon M. Jackson, Mehran Karimzadeh, Madeleine Arseneault, Pierre Lepage, Alexandre How-Kit, Antoine Daunay, Victor Renault, Hélène Blanché, Emmanuel Tubacher, Jeremy Sehmoun, Juris Viksna, Edgars Celms, Martins Opmanis, Andris Zarins, Naveen S. Vasudev, Morag Seywright, Behnoush Abedi-Ardekani, Christine Carreira, Peter J. Selby, Jon J. Cartledge, Graham Byrnes, Jiri Zavadil, Jing Su, Ivana Holcatova, Antonin Brisuda, David Zaridze, Anush Moukeria, Lenka Foretova, Marie Navratilova, Dana Mates, Viorel Jinga, Artem Artemov, Artem Nedoluzhko, Alexander Mazur, Sergey Rastorguev, Eugenia Boulygina, Simon Heath, Marta Gut, Marie-Therese Bihoreau, Doris Lechner, Mario Foglio, Ivo G. Gut, Konstantin Skryabin, Egor Prokhortchouk, Anne Cambon-Thomsen, Johan Rung, Guillaume Bourque, Paul Brennan, Jörg Tost, Rosamonde E. Banks, Alvis Brazma and G. Mark Lathrop ()
Additional contact information
Ghislaine Scelo: International Agency for Research on Cancer (IARC)
Yasser Riazalhosseini: McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, Canada H3A 1B1
Liliana Greger: European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus
Louis Letourneau: McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, Quebec, Canada H3A 0G1
Mar Gonzàlez-Porta: European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus
Magdalena B. Wozniak: International Agency for Research on Cancer (IARC)
Mathieu Bourgey: McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, Quebec, Canada H3A 0G1
Patricia Harnden: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James’s University Hospital
Lars Egevad: Karolinska Institutet
Sharon M. Jackson: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James’s University Hospital
Mehran Karimzadeh: McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, Canada H3A 1B1
Madeleine Arseneault: McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, Canada H3A 1B1
Pierre Lepage: McGill University and Genome Quebec Innovation Centre, 740 Doctor Penfield Avenue, Montreal, Quebec, Canada H3A 0G1
Alexandre How-Kit: Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain
Antoine Daunay: Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain
Victor Renault: Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain
Hélène Blanché: Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain
Emmanuel Tubacher: Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain
Jeremy Sehmoun: Fondation Jean Dausset - Centre d'Etude du Polymorphisme Humain
Juris Viksna: Institute of Mathematics and Computer Science, University of Latvia
Edgars Celms: Institute of Mathematics and Computer Science, University of Latvia
Martins Opmanis: Institute of Mathematics and Computer Science, University of Latvia
Andris Zarins: Institute of Mathematics and Computer Science, University of Latvia
Naveen S. Vasudev: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James’s University Hospital
Morag Seywright: The Beatson Institute for Cancer Research
Behnoush Abedi-Ardekani: International Agency for Research on Cancer (IARC)
Christine Carreira: International Agency for Research on Cancer (IARC)
Peter J. Selby: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James’s University Hospital
Jon J. Cartledge: Leeds Teaching Hospitals NHS Trust, Lincoln Wing, St James’s University Hospital
Graham Byrnes: International Agency for Research on Cancer (IARC)
Jiri Zavadil: International Agency for Research on Cancer (IARC)
Jing Su: European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus
Ivana Holcatova: First Faculty of Medicine, Institute of Hygiene and Epidemiology, Charles University in Prague
Antonin Brisuda: University Hospital Motol
David Zaridze: Russian N.N. Blokhin Cancer Research Centre
Anush Moukeria: Russian N.N. Blokhin Cancer Research Centre
Lenka Foretova: Masaryk Memorial Cancer Institute and MF MU
Marie Navratilova: Masaryk Memorial Cancer Institute and MF MU
Dana Mates: National Institute of Public Health
Viorel Jinga: Carol Davila University of Medicine and Pharmacy, Th. Burghele Hospital
Artem Artemov: Centre ‘Bioengineering’, The Russian Academy of Sciences
Artem Nedoluzhko: National Research Centre ‘Kurchatov Institute’
Alexander Mazur: Centre ‘Bioengineering’, The Russian Academy of Sciences
Sergey Rastorguev: National Research Centre ‘Kurchatov Institute’
Eugenia Boulygina: National Research Centre ‘Kurchatov Institute’
Simon Heath: Centro Nacional de Análisis Genómico
Marta Gut: Centro Nacional de Análisis Genómico
Marie-Therese Bihoreau: Centre National de Génotypage, CEA - Institute de Génomique
Doris Lechner: Centre National de Génotypage, CEA - Institute de Génomique
Mario Foglio: Centre National de Génotypage, CEA - Institute de Génomique
Ivo G. Gut: Centro Nacional de Análisis Genómico
Konstantin Skryabin: Centre ‘Bioengineering’, The Russian Academy of Sciences
Egor Prokhortchouk: Centre ‘Bioengineering’, The Russian Academy of Sciences
Anne Cambon-Thomsen: Faculty of Medicine, Institut National de la Santé et de la Recherche Medicale (INSERM) and University Toulouse III-Paul Sabatier, UMR 1027
Johan Rung: European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus
Guillaume Bourque: McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, Canada H3A 1B1
Paul Brennan: International Agency for Research on Cancer (IARC)
Jörg Tost: Centre National de Génotypage, CEA - Institute de Génomique
Rosamonde E. Banks: Leeds Institute of Cancer and Pathology, University of Leeds, Cancer Research Building, St James’s University Hospital
Alvis Brazma: European Molecular Biology Laboratory, European Bioinformatics Institute, EMBL-EBI, Wellcome Trust Genome Campus
G. Mark Lathrop: McGill University, 1205 Dr Penfield Avenue, Montreal, Quebec, Canada H3A 1B1

Nature Communications, 2014, vol. 5, issue 1, 1-13

Abstract: 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.

Date: 2014
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DOI: 10.1038/ncomms6135

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