Newly discovered biomarkers detect prostate cancer and predict recurrence

Volume 1, Issue 2, 2012
Krishna V. Donkena, Ph.D.

Krishna V. Donkena, Ph.D.

Alterations to the so-called on-off switches of genes occur early in the development of prostate cancer and could be used as biomarkers to detect the disease months or even years earlier than current approaches, a Mayo Clinic study has found. These biomarkers — known as DNA methylation profiles — also can predict if the cancer is going to recur and if that recurrence will remain localized to the prostate or, instead, spread to other organs. The study, published in the journal Clinical Cancer Research, is the first to capture the methylation changes that occur across the entire human genome in prostate cancer.

Senior author and Mayo Clinic Cancer Center molecular biologist Krishna V. Donkena, Ph.D., and her colleagues analyzed the methylation status of 14,495 genes from 238 prostate cancer patients. The patients included people who remained cancer-free after treatment, those who had a localized tumor recurrence and those whose cancer had spread. The researchers found that the DNA methylation changes that occurred during the earliest stages of prostate cancer development were nearly identical in all patients.

Having discovered DNA methylation patterns that could distinguish between healthy and cancerous tissue, the researchers then searched for similar biomarkers that could distinguish between patients with varying levels of recurrence risk. They found distinct methylation alterations that corresponded to whether a patient had a slow-growing tumor, known as an indolent tumor, or had a more aggressive one.

If physicians can determine what type of tumor patients have, they can avoid exposing patients with indolent tumors to unnecessary treatment and can treat those with aggressive tumors earlier and more effectively, Dr. Donkena said.

Dr. Donkena and her colleagues are working to develop a DNA methylation test that is more cost-effective and practical for use in clinical settings. The test currently relies on microarray or gene chip technology that assesses methylation status of genes across an entire genome. The researchers are trying to generate a more economical custom microarray to specifically look at only the genes that predict the development of prostate cancer or recurrence.

They also hope to develop drugs that can reverse DNA methylation in prostate cancer cells. Similar drugs are already being used to treat certain forms of leukemia.

Co-authors of the journal article are Saswati Mahapatra; Eric W. Klee, Ph.D.; Charles Y. Young, Ph.D.; Zhifu Sun, M.D.; Rafael E. Jimenez, M.D.; George G. Klee, M.D., Ph.D.; and Donald J. Tindall, Ph.D., all of Mayo Clinic. The American Cancer Society and the Department of Defense funded the study. For information about cancer clinical trials at Mayo Clinic, call 507-538-7623.

Mayo Clinic Researchers Discover Gene Biomarkers for Prostate Cancer Detection

Watch a video of Dr. Donkena discussing this study.