Mayo Clinic genomic analysis lends insight to prostate cancer

Volume 2, Issue 4, 2013

Summary

Prostate cancer tumors that are more aggressive have similar genetic origins, which may help in predicting cancer progression.

Photograph showing John C. Cheville, M.D., a Mayo Clinic pathologist

John C. Cheville, M.D.

Mayo Clinic Cancer Center researchers have used next-generation genomic analysis to determine that prostate cancer tumors that are more aggressive have similar genetic origins, a finding that may help predict cancer progression. The findings appeared in the June 1, 2013, online edition of the journal Cancer Research.

"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 John C. Cheville, M.D., Mayo Clinic pathologist and one of the authors on the paper.

The standard method of evaluating prostate cancer biopsy samples is a numerical scoring system called Gleason grading. In this method, a pathologist examines the tumor sample under the microscope, giving it a Gleason score based on the pattern of its cells.

Since many prostate cancers contain more than one pattern, 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 more aggressive prostate cancer.

The genomic analysis study focused on Gleason patterns of 3 and 4, or a Gleason score of 7, 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," Dr. 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, physicians may be better able to predict progression of the cancer and, in turn, better manage patients, including those who forgo treatment and instead enter a follow-up program called active surveillance.