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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Carcinoma, Renal Cell / genetics*
  • Cohort Studies
  • Europe
  • Female
  • Focal Adhesions / metabolism
  • Gene Expression Profiling
  • Gene Expression Regulation, Neoplastic
  • Genetic Variation*
  • Genome, Human / genetics*
  • Genomics*
  • Humans
  • Male
  • Middle Aged
  • Mutation
  • Mutation Rate
  • Oncogene Proteins, Fusion / genetics
  • Phosphatidylinositol 3-Kinases / genetics
  • RNA Splicing / genetics
  • Sequence Analysis, DNA
  • Signal Transduction / genetics


  • Oncogene Proteins, Fusion
  • Phosphatidylinositol 3-Kinases

Supplementary concepts

  • Clear-cell metastatic renal cell carcinoma