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Novel analyses improve identification of cancer-associated genes from microarray data
Date:5/2/2014

mpared to the frequency of identification that one could expect by pure chance. Across all four cancer types, the new method of selecting candidate genes based on inter-tumor variation in gene expression outperformed the other methods, including the standard method of comparing mean expression in adjacent normal and tumor tissues. Dr. Gorlov and colleagues also used this approach to identify novel cancer-associated genes.

The authors cite tumor heterogeneity as the most likely reason for the success of their variance-based approach. The method is based on the knowledge that different tumors can be driven by different subsets of cancer genes. By identifying genes with high variation in expression between tumors, the method preferentially identifies genes specifically associated with cancer. This same feature, tumor heterogeneity, may reduce the ability to identify critical gene expression changes when comparing mean gene expression in adjacent tumor and normal tissues, as tumors of the same type may have different sets of genes differentially expressed.

The results of the study challenge the model that comparing mean gene expression in adjacent normal and cancer tissues is the best approach to identifying cancer-associated genes. Indeed, the team identified high variation in adjacent "normal" tissue samples, which are typically used as control samples for comparison in analyses based on mean gene expression. The study suggests that methods based on variance may help get the most from existing and future global gene expression studies.


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Contact: Derik Hertel
derik.hertel@dartmouth.edu
603-650-1211
The Geisel School of Medicine at Dartmouth
Source:Eurekalert

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