Journal Article

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

Harnden, Patricia, Abedi-Ardekani, Behnoush, Selby, Peter J., Rung, Johan, Renault, Victor, Viksna, Juris, Zarins, Andris, Brazma, Alvis, Jackson, Sharon M., Gut, Marta, Seywright, Morag, Brisuda, Antonin, Foglio, Mario, Bourque, Guillaume, Scelo, Ghislaine, Cambon-Thomsen, Anne, Tubacher, Emmanuel, Mates, Dana, Jinga, Viorel, Bourgey, Mathieu, Artemov, Artem, Lathrop, G. Mark, Byrnes, Graham, Mazur, Alexander, Lepage, Pierre, Moukeria, Anush, Navratilova, Marie, Gut, Ivo G., Egevad, Lars, Zavadil, Jiri, Vasudev, Naveen S., Celms, Edgars, How-Kit, Alexandre, Bihoreau, Marie-Therese, Wozniak, Magdalena B., Holcatova, Ivana, Opmanis, Martins, Boulygina, Eugenia, Greger, Liliana, Daunay, Antoine, Cartledge, Jon J., Zaridze, David, Skryabin, Konstantin, Tost, Jörg, Foretova, Lenka, Brennan, Paul, Rastorguev, Sergey, Sehmoun, Jeremy, Arseneault, Madeleine, Nedoluzhko, Artem, Blanché, Hélène, Su, Jing, Prokhortchouk, Egor, Letourneau, Louis, Karimzadeh, Mehran, Carreira, Christine, Lechner, Doris, Gonzàlez-Porta, Mar, Heath, Simon, Banks, Rosamonde E., Riazalhosseini, Yasser

2014

Overview

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. Renal cancer accounts for 2.4% of all adult cancers and its incidence is increasing worldwide. Here, the authors carry out genome and transcriptome sequencing of clear cell renal cell carcinomas (ccRCCs) and highlight genomic aberrations and biological pathways underlying ccRCC tumorigenesis.

• Publisher: Nature Publishing Group UK,Nature Publishing Group
• Subject: 631/208/69 / 631/67/2324 / 631/67/589/1588/1351 / Adult / Aged / Aged, 80 and over / Biochemistry, Molecular Biology / Cancer research / Carcinoma, Renal Cell - genetics / Cohort Studies / Epidemiology / Epigenetics / Europe / Female / Focal Adhesions - metabolism / Gene Expression Profiling / Gene Expression Regulation, Neoplastic / Genetic Variation / Genome, Human - genetics / Genomes / Genomics / Hospitals / Humanities and Social Sciences / Humans / Kidney cancer / Life Sciences / Male / Medical research / Middle Aged / multidisciplinary / Mutation / Mutation Rate / Oncogene Proteins, Fusion - genetics / Pathology / Phosphatidylinositol 3-Kinases - genetics / Public health / RNA Splicing - genetics / Science / Science (multidisciplinary) / Sequence Analysis, DNA / Signal Transduction - genetics