Integration of whole genome SNP mapping and transcriptional data in clear renal cell carcinoma primary cell cultures

Renal cell carcinomas (RCCs) comprise a heterogeneous group of tumors representing 2%-3% of all adult cancers. Among RCCs, the clear cell histotype (cRCC) is the most common, representing 80% of all primary renal neoplasias. cRCC can be familial or sporadic, with recurrent genomic deletions or translocations, suggesting that genetic mechanisms are involved in early tumorigenesis. In the context of an Italian research oncological project aimed to the identification of new molecular markers for cRCC at different tissues levels using an integrated molecular approach (DNA/RNA/protein), we performed a whole transcriptome/genome integrated analysis of primary cell cultures prepared from tumor, cortical and medullar surgical tissues using the Affymetrix microarray technology. In particular we use either U133 Plus 2.0 and Human Mapping 10K GeneChips® that allow the analysis of 54.000 human transcripts and 11.550 Single Nucleotide Polymorphisms (SNP) distributed over all human chromosomes respectively. Results of gene expression profiling of cRCC versus Universal Human Reference RNA (hRefRNA) highlight a total of 829 modulated transcripts (393 down- and 436 up- regulated). Cortex tissues show 961 modulated transcripts compared with hRefRNA (213 down- and 748 up-regulated), whereas medullar tissues evidence 824 modulated transcripts (220 down- and 604 up-regulated). Analysis of genomic instability on triads of RCC primary cultures–tumor biopsies–normal blood samples is in progress. A complex data mining strategy for integrating whole transcriptome/genome results using several bionformatics tools (GCOS, GDAS, Copy Number Tool, dCHIP, GenMAPP, IGB, DAVID, PubMATRIX ) will be shown. This work was supported by MIUR-FIRB grants n°RBNE01HCKF and n°RBNE01TZZ8.