title: Higher gene expression variability in the more aggressive subtype of chronic lymphocytic leukemia.
abstract: BACKGROUND
  Chronic lymphocytic leukemia (CLL) presents two subtypes which have drastically different clinical outcomes, IgVH mutated (M-CLL) and IgVH unmutated (U-CLL). So far, these two subtypes are not associated to clear differences in gene expression profiles. Interestingly, recent results have highlighted important roles for heterogeneity, both at the genetic and at the epigenetic level in CLL progression.
  
  
  METHODS
  We analyzed gene expression data of two large cohorts of CLL patients and quantified expression variability across individuals to investigate differences between the two subtypes using different measures and statistical tests. Functional significance was explored by pathway enrichment and network analyses. Furthermore, we implemented a random forest approach based on expression variability to classify patients into disease subtypes.
  
  
  RESULTS
  We found that U-CLL, the more aggressive type of the disease, shows significantly increased variability of gene expression across patients and that, overall, genes that show higher variability in the aggressive subtype are related to cell cycle, development and inter-cellular communication. These functions indicate a potential relation between gene expression variability and the faster progression of this CLL subtype. Finally, a classifier based on gene expression variability was able to correctly predict the disease subtype of CLL patients.
  
  
  CONCLUSIONS
  There are strong relations between gene expression variability and disease subtype linking significantly increased expression variability to phenotypes such as aggressiveness and resistance to therapy in CLL.
authors: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
authors: Simone
authors: S
authors: Ecker
authors: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
authors: Vera
authors: V
authors: Pancaldi
authors: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
authors: Daniel
authors: D
authors: Rico
authors: Structural Biology and Biocomputing Programme, Spanish National Cancer Research Center (CNIO), 28029 Madrid, Spain.
authors: Alfonso
authors: A
authors: Valencia
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