Similar genetic origins for some aggressive prostate cancers

Next generation genomic analysis has determined that some of the more aggressive prostate cancers have similar genetic origins, according to a recent publication. This information may help in predicting cancer progression.

"This is the first study to examine DNA alterations using next generation sequencing in adjacent Gleason patterns in the same tumor, allowing us to correlate genomics with changes in pathology," said pathologist and study author John Cheville, MD, of the Mayo Clinic in Rochester, Minnesota.

Prostate cancer biopsy samples are evaluated by Gleason grading. This is a numerical scoring system in which a pathologist examines the tumor sample under a microscope and gives it a Gleason score based on the pattern of its cells. Many prostate cancers contain more than one pattern, and so the two most common patterns are added together to provide the Gleason score.

The Gleason score is the strongest predictor of outcome, with high scores indicating a more aggressive prostate cancer. This study focused on Gleason patterns of three and four (Gleason score seven), which is a combination that indicates a cancer with increased risk of progression.

"While each pattern had its own breakpoints, they shared identical ones, which implies a common origin," Cheville said. DNA changes associated with aggressive prostate cancer were identified in the lower Gleason pattern, indicating that genomic changes occurred before they could be recognized by a pathologist. By understanding these lineage relationships within a tumor, he said, physicians will be better able to predict progression of the cancer and, in turn, better manage patients including those who chose no treatment but entered a follow-up program called active surveillance.

To determine relationships among the Gleason patterns of each tumor sample the team used laser capture micro-dissection, whole genome amplification, and next generation sequencing. They examined 14 tumors and found over 3,000 unique chromosomal alterations among all tumors and 300 that appeared in at least two of the tumors.

They also found that Gleason pattern three in each tumor had more alterations in common with its corresponding Gleason pattern four than it did with Gleason pattern three from other patients. This research was published in Cancer Research (2013; doi: 10.1158/0008-5472.CAN-12-2803).
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