Full genetic blueprint of multiple prostate tumors unveiled

LONDON - Scientists have for the first time laid bare the full genetic blueprint of multiple prostate tumors, uncovering alterations that have never before been detected and offering a deep view of the genetic missteps that underlie the disease.

The work was led by researchers from Weill Cornell Medical College, the Broad Institute, and the Dana-Farber Cancer Institute.

The study, made possible by key advances in whole genome sequencing and analysis, points to several new prostate cancer genes and a critical category of genomic changes as important drivers of prostate cancer growth.

Unlike other sequencing methods that target specific sections of the genome, whole genome sequencing enables researchers to look across the entire DNA landscape of a tumor, making it possible to discern global changes and patterns.

Senior authors Drs. Levi Garraway and Mark Rubin and their colleagues used this strategy to view the complete genomes of seven prostate tumors and compare them to normal tissue samples to find regions of abnormality.

“Whole genome sequencing gives us fascinating new insights into a category of alterations that may be especially important in prostate cancer,” says Dr. Garraway, a senior associate member of the Broad Institute and a medical oncologist and assistant professor at the Dana-Farber and Harvard Medical School.

Dr. Rubin compares the Nature study to looking not just for spelling errors in the genome, but also for whole paragraphs or sections of genomic text that have been rearranged.

“One of the big surprises is the fact that prostate cancer doesn’t have a large number of misspellings, but instead has a large, significant number of rearrangements,” says Dr. Rubin.

“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.”

These alterations are known as genomic rearrangements - a kind of shuffling that occurs when a piece of DNA from one part of the genome breaks off and reattaches itself in another location. These rearrangements can create new genes (called “fusion genes”), allow a gene to operate unchecked, or prevent a gene from even working at all.
uch changes can set a cell on a path toward cancer. By looking for genes affected by these rearrangements in multiple prostate cancer samples, the researchers unearthed new genes tied to the disease and found new mechanisms that may be driving cancer as a whole.

“This first whole genome view shows us tantalizing evidence for several new prostate cancer genes that likely would have remained undiscovered had we not been taking a genome-wide approach,” says Dr. Garraway.

The study appears in the Feb. 10th issue of the journal Nature. (ANI)