Abstract
<h3>Abstract</h3> Oncogenes promote the development of and serve as therapeutic targets against subsets of cancers. Here, a new statistical approach that captures transcriptional heterogeneity in tumor and adjacent normal (i.e. tumor-free) mRNA expression profiles was developed to identify oncogene candidates that were overexpressed in a subset of breast tumors. Intronic DNA methylation was strongly associated with the overexpression of chromobox 2 (<i>CBX2</i>), an oncogene candidate that was identified using our method but not through prior analytical approaches. <i>CBX2</i> overexpression in breast tumors was associated with the upregulation of genes involved in cell cycle progression and is associated with poorer 5-year survival. The predicted function of <i>CBX2</i> was confirmed <i>in vitro</i> providing the first experimental evidence that <i>CBX2</i> promotes breast cancer cell growth. Modeling mRNA expression heterogeneity in tumors is a novel powerful approach with the potential to uncover therapeutic targets that benefit subsets of cancer patients.
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