Genome sequencing uncovers prostate tumor alterations

A recent study has uncovered alterations that have never been detected in prostate tumors and offer a deep view of the genetic missteps that underlie the disease, according to scientists from two U.S. institutions.

The study, published in Nature (2011; 470:214-20), points to several new prostate cancer genes and a critical category of genomic changes as important drivers of prostate cancer growth. The research was made possible by key advances in whole genome sequencing and analysis.

Senior authors Levi Garraway, MD, and Mark Rubin, MD, and their colleagues viewed the complete genomes of seven prostate tumors and compared them with normal tissue samples to find regions of abnormality.

"We would never have guessed that there were so many genomic alterations of this type before now because we didn’t have the right tools to look for them," added Dr. Rubin, of Weill Cornell Medical College and New York-Presbyterian Hospital/Weill Cornell Medical Center, New York.

By looking for genes affected by genomic rearrangements in multiple prostate cancer samples, the team unearthed new genes tied to the disease and found new mechanisms that may be driving cancer as a whole.

In addition to uncovering new and suspected genes, the researchers say whole genome sequencing has given them insights into how genomic rearrangements arise in the first place. The authors looked for breaks and reattachments and found that these events are not distributed randomly across the genome. Rather, in some tumors these events take place in areas of the genome that are inactive or silent, while in other tumors they occur in regions that are highly active. This pattern suggests that mistakes made by cells while turning genes on and off might give rise to DNA rearrangements and therefore play a formative role in cancer’s development.

"This study could enhance our ability to develop new, diagnostic markers for prostate cancer," Dr. Rubin said. "We can also imagine eventually developing more personalized diagnostic tools for patients with recurrent tumors, to essentially follow the tumors’ progression by testing for new genomic alterations."

"Many of these features were invisible before," Dr. Garraway said. "Now, we’re realizing that by sequencing whole genomes in prostate cancer, there’s a lot more to see. These discoveries are teaching us a great deal about prostate cancer biology that we simply hadn’t appreciated previously."