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:T4T: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.

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We have investigated the apoptotic levels and expression of the apoptotic inducer Bak in non-melanoma skin cancers. Squamous cell carcinomas of known human papillomavirus status from immunocompetent patients were analysed for the expression of the Bak protein, and the expression profile was compared both to the presence of apoptotic cells and the proliferation marker Ki-67. We demonstrate an inverse correlation between human papillomavirus positivity and Bak expression in squamous cell carcinomas, with concomitantly fewer apoptoic cells being detected in the human papillomavirus positive tumours. Bak expression was not observed in basal cell carcinomas irrespective of human papillomavirus status, suggesting that Bak only plays a role in signalling apoptosis in squamous, but not basal, cell cancers. No differences were observed in the proliferation rates between papillomavirus positive and negative squamous cell tumours. However, a significant decrease in the number of apoptotic cells was observed in human papillomavirus-positive squamous cell carcinomas which suggests that the virus may have significantly altered the relationship between proliferation and apoptosis in a proportion of these tumours.