A novel systems-based approach that combines comprehensive gene expression profiling with genome-wide transcription factor analysis and protein-protein interaction has led researchers to an important genetic marker that can help physicians know which breast cancer patients are at highest risk and will require more aggressive treatment, a research team based at the University of Chicago Medical Center reports in the April 15, 2008, issue of the journal Molecular Systems Biology.
The researchers found that high expression of a protein known as H2A.Z, which is associated with the expression of genes within the nucleus, can help physicians predict which patients are most at risk for disease spread and death. It could also serve as a new target for therapy.
Elevated H2A.Z expression is significantly associated with metastasis and shorter survival, and it could quickly help doctors make better predictions and treatment choices for their patients, said study director Kevin White, PhD, professor of human genetics and director of the Institute for Genomics and Systems Biology at the University of Chicago and Argonne National Laboratory. It could also provide clues to new therapies.
But, perhaps more important, he added, we think we have developed an integrated approach to genomic analysis that can be applied to a wide range of cancers.
Instead of a standard whole-genome analysis, looking for genetic variations that correlate with disease risk, White and colleagues integrated multiple genetic technologies to measure the effects of estrogens, which play a crucial role in many breast cancers, on multiple cellular pathways, what they refer to as a transcriptional regulatory cascade.
The female hormone estrogen acts by binding to the estrogen receptor, which carries the hormones signal to a cells nucleus, where it activates many other genes. One of those genes is a known cancer-related gene called c-MYC, which in turn regulate
|Contact: John Easton|
University of Chicago Medical Center