The goal of this analysis was to develop a computational tool that integrates the totality of gene expression,
DNA copy number, and sequence abnormalities in individual
cancers in the framework of biological processes. We used the hierarchical structure of the gene ontology (GO) database to create a reference network and projected
mRNA expression,
DNA copy number and mutation anomalies detected in single samples into this space. We applied our method to 59 breast
cancers where all three types of molecular data were available. Each
cancer had a large number of disturbed biological processes. Locomotion, multicellular organismal process, and signal transduction pathways were the most commonly affected GO terms, but the individual molecular events were different from case-to-case.
Estrogen receptor-positive and -negative
cancers had different repertoire of anomalies. We tested the functional impact of 27 mRNAs that had overexpression in
cancer with variable frequency (<2-42 %) using an
siRNA screen. Each of these genes inhibited cell growth in at least some of 18
breast cancer cell lines. We developed a free, on-line software tool ( http://netgoplot.org ) to display the complex genomic abnormalities in individual
cancers in the biological framework of the GO biological processes. Each
cancer harbored a variable number of pathway anomalies and the individual molecular events that caused an anomaly varied from case-to-case. Our in vitro experiments indicate that rare case-specific molecular abnormalities can play a functional role and driver events may vary from case-to-case depending on the constellation of other molecular anomalies.