Scientists identified five additional genes that fuse to ERG or ETV1 to induce the disease.
Researchers at the University of Michigan Comprehensive Cancer Center discovered that pieces of two chromosomes can trade places with each other and cause two genes to fuse together. The fused genes then override the off switch that keeps cells from growing uncontrollably, causing prostate cancer to develop.
“Each of these switches, or gene fusions, represent different molecular subtypes,” explains lead study author Arul Chinnaiyan, M.D., Ph.D., director of the Michigan Center for Translational Pathology. “This tells us there’s not just one type of prostate cancer. It’s a more complex disease and potentially needs to be treated differently in each patient.”
In 2005, the scientists identified a prostate-specific gene called TMPRSS2, which fuses with either ERG or ETV1, two genes known to be involved in several types of cancer. In the current study, they found five additional genes that fuse with ERG or ETV1. The team report that when they tested these gene fusions in mice and in cell cultures and results showed that the fusions are what cause prostate cancer to develop.
The investigators found that gene fusions were involved in 60–70% of the prostate cancer cell lines they looked at. The genes involved are all controlled by a different mechanism; for example, four of the genes are regulated by androgen, a male sex hormone known to fuel prostate cancer.
The results of the study appear in the August 2 issue of Nature.
