title: Integrative genome-wide expression profiling identifies three distinct molecular subgroups of renal cell carcinoma with different patient outcome.
abstract: BACKGROUND
  Renal cell carcinoma (RCC) is characterized by a number of diverse molecular aberrations that differ among individuals. Recent approaches to molecularly classify RCC were based on clinical, pathological as well as on single molecular parameters. As a consequence, gene expression patterns reflecting the sum of genetic aberrations in individual tumors may not have been recognized. In an attempt to uncover such molecular features in RCC, we used a novel, unbiased and integrative approach.
  
  
  METHODS
  We integrated gene expression data from 97 primary RCC of different pathologic parameters, 15 RCC metastases as well as 34 cancer cell lines for two-way nonsupervised hierarchical clustering using gene groups suggested by the PANTHER Classification System. We depicted the genomic landscape of the resulted tumor groups by means of Single Nuclear Polymorphism (SNP) technology. Finally, the achieved results were immunohistochemically analyzed using a tissue microarray (TMA) composed of 254 RCC.
  
  
  RESULTS
  We found robust, genome wide expression signatures, which split RCC into three distinct molecular subgroups. These groups remained stable even if randomly selected gene sets were clustered. Notably, the pattern obtained from RCC cell lines was clearly distinguishable from that of primary tumors. SNP array analysis demonstrated differing frequencies of chromosomal copy number alterations among RCC subgroups. TMA analysis with group-specific markers showed a prognostic significance of the different groups.
  
  
  CONCLUSIONS
  We propose the existence of characteristic and histologically independent genome-wide expression outputs in RCC with potential biological and clinical relevance.
authors: Institute of Surgical Pathology, University Hospital Zurich, Schmelzbergstrasse 12, 8091, Zurich, Switzerland. manfred.beleut@pareq.com
authors: Manfred
authors: M
authors: Beleut
authors: Philip
authors: P
authors: Zimmermann
authors: Michael
authors: M
authors: Baudis
authors: Nicole
authors: N
authors: Bruni
authors: Peter
authors: P
authors: Bühlmann
authors: Oliver
authors: O
authors: Laule
authors: Van-Duc
authors: VD
authors: Luu
authors: Wilhelm
authors: W
authors: Gruissem
authors: Peter
authors: P
authors: Schraml
authors: Holger
authors: H
authors: Moch
mesh_terms: D002292:Carcinoma, Renal Cell / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D045744:Cell Line, Tumor; D016000:Cluster Analysis; D056915:DNA Copy Number Variations; D020869:Gene Expression Profiling; D006801:Humans; D007680:Kidney Neoplasms / Q000145:classification* / Q000235:genetics / Q000401:mortality / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D011379:Prognosis; D016016:Proportional Hazards Models