title: 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.
  
  
  RESULTS
  We performed the first integrated analysis of DNA and RNA profiles of RCC samples using Affymetrix technology. Using 100K SNP mapping arrays, we assembled a genome-wide map of DNA copy number alterations and LOH areas. We thus confirmed the typical genetic signature of RCC but also identified other amplified regions (e.g. on chr. 4, 11, 12), deleted regions (chr. 1, 9, 22) and LOH areas (chr. 1, 2, 9, 13). Simultaneously, using HG-U133 Plus 2.0 arrays, we identified differentially expressed genes (DEGs) in tumor vs. normal samples. Combining genomic and transcriptomic data, we identified 71 DEGs in aberrant chromosomal regions and observed, in amplified regions, a predominance of up-regulated genes (27 of 37 DEGs) and a trend to clustering. Functional annotation of these genes revealed some already implicated in RCC pathology and other cancers, as well as others that may be novel tumor biomarkers.
  
  
  CONCLUSIONS
  By combining genomic and transcriptomic profiles from a collection of RCC samples, we identified specific genomic regions with concordant alterations in DNA and RNA profiles and focused on regions with increased DNA copy number. Since the transcriptional modulation of up-regulated genes in amplified regions may be attributed to the genomic alterations characteristic of RCC, these genes may encode novel RCC biomarkers actively involved in tumor initiation and progression and useful in clinical applications.
authors.affiliation: Dept. of Biomedical Sciences and Technologies and CISI, University of Milan, Milan, Italy. ingrid.cifola@unimi.it
authors.forename: Ingrid
authors.initials: I
authors.lastname: Cifola
authors.forename: Roberta
authors.initials: R
authors.lastname: Spinelli
authors.forename: Luca
authors.initials: L
authors.lastname: Beltrame
authors.forename: Clelia
authors.initials: C
authors.lastname: Peano
authors.forename: Ester
authors.initials: E
authors.lastname: Fasoli
authors.forename: Stefano
authors.initials: S
authors.lastname: Ferrero
authors.forename: Silvano
authors.initials: S
authors.lastname: Bosari
authors.forename: Stefano
authors.initials: S
authors.lastname: Signorini
authors.forename: Francesco
authors.initials: F
authors.lastname: Rocco
authors.forename: Roberto
authors.initials: R
authors.lastname: Perego
authors.forename: Vanessa
authors.initials: V
authors.lastname: Proserpio
authors.forename: Francesca
authors.initials: F
authors.lastname: Raimondo
authors.forename: Paolo
authors.initials: P
authors.lastname: Mocarelli
authors.forename: Cristina
authors.initials: C
authors.lastname: Battaglia
mesh_terms: D014408:Biomarkers, Tumor / Q000235:genetics*; D002292:Carcinoma, Renal Cell / Q000235:genetics*; D018628:Gene Dosage; D015870:Gene Expression; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics*; D019656:Loss of Heterozygosity; D020641:Polymorphism, Single Nucleotide
chemical_list: D014408:Biomarkers, Tumor