Investigators found a gene fusion that is highly expressed in a subset of prostate cancers and can be found in urine. They add that this gene fusion, SLC45A3-ELK4, may represent an entirely new mechanism that cancer cells use to grow.
Unlike the gene fusions previously found in cancers, which arise when two chromosomes join together in an abnormal way, the new fusion occurs when the genes are being copied into RNA. The two genes, SLC45A3 and ELK4, reside next to one another on the chromosome in normal and prostate cancer cells. When the genes are copied into RNA in the prostate cancer cells, however, they frequently generate a single RNA message that fuses information from both genes.
The team is trying to figure out the implications of this discovery, but stress that the diagnostic implications are more immediate. They say that these types of genetic chimera occur at significantly higher levels in abnormal tumor cells.
“We think this is going to be a potentially important diagnostic marker in prostate cancer,” says senior author Mark A. Rubin, M.D., the Homer T. Hirst professor of oncology in pathology, professor of pathology and laboratory medicine, and vice chair for experimental pathology at Weill Cornell Medical College.
Dr. Rubin's team is working with a company to develop a urine test for prostate cancer using a chromosome-based gene fusion called TMPRSS2-ERG. He anticipates that the newly discovered SLC45A3-ELK4 gene fusion may be added to that urine test in the future to increase its accuracy and also to potentially help determine the level of response to certain nonsurgical systemic treatments.
The latest study is reported in the April 1 issue of Cancer Research and was done by scientists at Weill Cornell Medical College, CHU Mondor, Ulm University Hospital, and the Brigham and Women's Hospital.