Genome-wide screening of copy number alterations and LOH events in renal cell carcinomas and integration with gene expression profile

Abstract

Background: Clear cell renal carcinoma (RCC) is the most common and invasive adult renal cancer. For the purpose of identifying RCC biomarkers, we investigated chromosomal regions and individual genes modulated in RCC pathology. We applied the dual strategy of assessing and integrating genomic and transcriptomic data, today considered the most effective approach for understanding genetic mechanisms of cancer and the most sensitive for identifying cancer-related genes.

Differential protein profiling of renal cell carcinoma urinary exosomes

“…46 Loss or decrease in neprilysin expression has been reported in many types of malignancies, including renal cancer. 34,47 DPEP1 and CD10 demonstrate to have a reduced content in RCC UE, compared to control ones, possibly according to the loss of the cellular specialization, as already mentioned. Finally, the levels of CAIX and CP are found significantly increased in RCC urinary exosomes: it has to be underlined that their promoters were reported to be activated by the transcriptional factor HIF-1a, known to be involved in RCC genesis.…”

“…Protein selection was based on several criteria including (1) our previous results obtained by gene and protein expression profiling on RCC tissue samples; 26,34 (2) their potential roles in contributing to RCC diagnosis, and (3) the availability of commercial antibodies. Based on the above criteria, we selected a panel of 10 proteins, and subjected their UE differential content to validation using western blot analysis (Fig.…”

“…Finally, the levels of CAIX and CP are found significantly increased in RCC urinary exosomes: it has to be underlined that their promoters were reported to be activated by the transcriptional factor HIF-1a, known to be involved in RCC genesis. [48][49][50] In particular, gene expression profiling on renal tissue showed a marked CP mRNA overexpression in RCC patients compared to controls, 34,51 while CAIX is proven to be a powerful tissue marker for ccRCC and was recently shown to correlate with tumor size. 52 Both CP and CAIX have been detected in RCC patient serum.…”

Molecular Portrait of Clear Cell Renal Cell Carcinoma: An Integrative Analysis of Gene Expression and Genomic Copy Number Profiling

“…To assess copy number alterations in ccRCC, we used two datasets composed of 27 sporadic ccRCC samples profiled by Affymetrix Human Mapping 100K SNP arrays and downloaded from AE (E-TAM-283, E-TAM-284; Cifola et al, 2008) and 26 sporadic ccRCC samples profiled by Affymetrix Human Mapping 250K Sty SNP array and downloaded from GEO (GSE14994; Beroukhim et al, 2009). The genomic copy number values were quantified using Partek Genomics Suite and the presence of copy number alterations, i.e., chromosomal segments affected by amplification or deletion, was calculated using Partek Genomic Segmentation (GS) algorithm.…”

“…Moreover, high-density single nucleotide polymorphism (SNP) array technology, interrogating thousands of SNP markers distributed throughout the whole human genome, has significantly improved the detection of chromosomal aberrations and offered the opportunity to detect regions with loss of heterozygosity (LOH), an important information for the identification of novel tumor suppressor genes. SNP-arrays have been widely applied to characterize tumor genomic instability (Brenner & Rosenberg, 2010;Lisovich, 2011) and recently to perform the genomewide DNA profiling of ccRCC tissue samples (Beroukhim, 2009;Cifola, 2008). Overall, ccRCC is characterized by recurrent genetic anomalies at characteristic chromosomes, such as deletions with LOH on chromosomes 3p (involving also the VHL locus), 6q, 8p, 9p, and 14q, and duplications of chromosomes 5q and 7.…”