Abstract 5103: Transcriptional profiling in clear cell renal cell carcinoma (ccRCC). Focus on Czech Republic
Authors: Wozniak Magdalena B. , Calvez-Kelm Florence Le , Lesueur Fabienne , Abedi-Ardekani Behnoush , Holcatova Ivana , Janout Vladimir , Foretova Lenka , Carreira Christine , Durand Geoffroy , Michelon Jocelyne , McKay James , Brennan Paul , Scelo Ghislaine 
Published: August 2012

Abstract
Renal cell carcinoma (RCC) is a poorly documented cancer, although time trends and geographical variations in incidence are intriguing. In addition to the frequent VHL mutation, recent studies have identified novel somatic alterations involved in RCC pathogenesis. Microarray and next generation sequencing efforts have been mostly performed on North American and Western European populations, while the highest incidence rates are found in Central/Eastern Europe. Our project has focused on the delineation of gene expression patterns specific to the Czech Republic population, where the incidence rates are the highest in the world. As a feasibility study, we performed whole genome expression profiling on 12 pairs of fresh frozen conventional clear cell RCC (ccRCC) tumors and adjacent non-tumor renal tissue using the Illumina HumanHT-12 v4 Expression BeadChips. To identify genes differentially expressed in ccRCC tumor versus normal tissue samples, the Significance Analysis of Microarrays (SAM) was used. Gene set enrichment analysis (GSEA) software was used for analysis of differentially expressed BioCarta categories and pathways associated with ccRCC pathogenesis. Following initial analyses a signature composed of 994 downregulated and 872 upregulated genes was found in ccRCC compared with normal tissue (FDR&lt;0.0001). Interestingly, approximately 25% of significantly downregulated genes were involved in cellular transport and homeostasis, these included aquaporins and solute carrier family of genes responsible for electrolyte, glucose, amino acid and fatty acid transport. In addition, several major proteins involved in renal development were found to be downregulated. The genes upregulated in ccRCC were involved in immune response, such as T-cell receptor (TCR), inflammatory and Toll-like receptor signaling as well as cell cycle regulation and NF-κB activation. Consistently with the results as outlined above, GSEA analysis demonstrated TCR, IL12, IL10, CTLA4, ATM, NFKB, VEGF pathway enrichment in the ccRCC as compared to normal kidney tissue (FDR&lt;0.2). Molecular analysis of ccRCC, facilitated by the comparison with normal renal tissue, highlighted the involvement of biological pathways not previously described in kidney carcinogenesis. Analysis of a larger set of 100 tumor/normal pairs from Czech ccRCC patients is underway. Further comparison of the identified gene expression signature characteristic for Czech ccRCC patients with expression profiles of other European and American series will identify possible novel genes and pathways involved in ccRCC pathogenesis.
Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5103. doi:1538-7445.AM2012-5103