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

Molecular Cancer
Ingrid CifolaCristina Battaglia

Abstract

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. 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 gene...Continue Reading

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Datasets Mentioned

BETA
E-TABM-283
E-TABM-284

Methods Mentioned

BETA
genotyping
array technology
electrophoresis
chip

Software Mentioned

ArrayExpress
CNAG
dChip2006
DAVID
MILANO
TIGR Multiple Experiment Viewer ( TMEV
UCSC genome browser
Copy Number Analyzer for GeneChip software ( CNAG
SAM

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