A new finding from researchers from the New York-Presbyterian Hospital/Weill Cornell Medical Center (New York) could lead to a radically different way for doctors and clinicians to screen for prostate cancer. Researchers have reported discovering a new gene fusion called NDRG1-ERG that is highly expressed in a subset of prostate cancers. In time, screening for the gene fusion occurrence could eventually surpass using Prostate Specific Antigen (PSA) screenings in cancer.
Gene fusions are a hybrid gene formed from two previously separated genes and are believed to be at the root of what causes cancer cells to grow more quickly than normal cells.
The new findings, were published in the August issue of the journal Neoplasia, and are different because unlike two previous fusions co-discovered by the same Weill Cornell Medical College laboratory group; this fusion can produce a protein that could be a potential target for drug therapies.
"The prostate cancer gene fusions, and proteins they produce, are important because they serve as a cancer-specific marker," Mark Rubin, PhD, vice chair for experimental pathology at Weill Cornell Medical College told Medical Device Daily.
He added that the current discovery is "unlike" PSAs and that "Currently, PSA testing is the standard of care, yet it is not accurate enough to predict prostate cancer, because many men may have an elevated PSA level, but have benign conditions such as inflammation of the prostate. With our new findings if you have the gene fusion [sequence] present, then you have cancer."
Also most of the gene fusions previously found in prostate cancer, the two genes, NDRG1 and ERG, likely produce a cancer-specific protein through genetic rearrangements. This fusion and protein are only found in cancer cells, and not within normal cells. Ongoing work is exploring the potential biologic implications of this discovery. However, the diagnostic implications are more immediate because these types of genetic chimera occur only in cancer.
"We think this type of gene fusion might be a common mechanism in other cancers," Rubin says. "This expands our understanding of how prostate tumor cells can hijack androgen-regulated genes by using neighboring genes to effectively alter their regulation. This may be a way tumors gain a competitive advantage over normal tissue."
To discover this new class of gene fusion the researchers used a pair-end digital sequencing of messenger RNA – the message that calls cells to produce. A team led by Mark Gerstein from Yale University (New Haven, Connecticut) and Andrea Sboner from Weill Cornell Medical College, were able to identify messages that emanated from two separate genes.
The researchers used technology from Gen-Probe (San Diego) a biotechnology diagnostics company to develop the urine tests to screen for the gene fusions.
But the key question is what affect this will have on PSAs and clinicians determination to continue using them. At this point Rubin said it is hard to tell whether PSA screenings will be replaced, but there ought to be a migration toward a more effective means of cancer detection.
"PSA is so ingrained in our clinical culture that it will take a while to get away from it," Rubin said. "While it's so useful in some settings as a screening tool it is outdated."
In the mean time, he said that these most recent findings could be the launch pad to move away from conventional cancer detection methods.
"In the future, these fusions, specific to certain types of prostate cancer, may help physicians prescribe tailored therapies for their patients by avoiding the trial and error that is often associated with cancer treatments," said Rubin.
He added that "We believe this is a first step toward providing patients with specific therapies that target individual cancer variants, and hope these findings will help doctors diagnose a patient's specific disease."