Advanced prostate cancer tumors have similar genetic origins

Researchers using next-generation genomic analysis have determined that some of the more aggressive prostate cancer tumors have similar genetic origins, which 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 co-author John Cheville, MD, of Mayo Clinic, Rochester, MN.

The study, which was published in Cancer Research (2013; 73:3275-84), focused on Gleason patterns of 3 and 4 (Gleason score 7).

"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, Dr. Cheville said, physicians will be better able to predict progression of the cancer and, in turn, better manage patients, including those who choose active surveillance.

To determine relationships among the Gleason patterns of each tumor sample, the authors 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 3 in each tumor had more alterations in common with its corresponding Gleason pattern 4 than it did with Gleason pattern 3 from other patients.

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