Genomic profiling of chromosomal instability in renal carcinoma primary cultures and cell lines by SNP array technology

The work described in this PhD thesis aimed to characterize 9 clear cell renal carcinoma primary cultures (RCCpc) and their parental tumor tissues and 5 commercial RCC cell lines, using the Affymetrix GeneChip® SNP array technology (50K and 250K platforms). We performed a genome-wide analysis of copy number alterations (CNAs) and LOH events, together with allele dosage, using CNAG (v3.0) and Affymetrix GTC (v2.0) software. RCCpc and parental tumor tissues were assessed comparing each culture and parental tissue to its corresponding blood sample, while cell lines were analyzed using 48 HapMap CEU samples as normal controls. Also, a comparison was performed between these samples and the typical RCC genomic signature, in order to assess if primary cultures and cell lines were a good in vitro model to study this pathology. The results here obtained indicated that our RCCpc were a reliable model to study RCC pathology, much better than RCC cell lines. Also, comparing RCCpc and parental tumor tissues, we demonstrated that RCCpc provided greater cell homogeneity and an enrichment in tumor cells with respect to heterogeneous bioptic tissues, thus facilitating the characterization of CNAs and the identification of novel genetic elements potentially involved in RCC etiology and useful in clinical applications.