Tumor DNA Testing Can Improve Lynch Syndrome Detection Rejects Age Limitations on Testing

December 16, 2015
Illustration of DNA testing process for Lynch syndrome in endometrial cancer

COLUMBUS, Ohio -- New research from The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute (OSUCCC) suggests many cases of Lynch syndrome could go undetected with current recommendations for age restrictions and testing methods.

Lynch syndrome is an inherited genetic condition that predisposes mutation carriers to certain cancers, most commonly colon and endometrial but also ovary, stomach and other gastrointestinal/liver tract cancers.

In this new study, researchers show that 24 percent of Lynch syndrome mutation carriers were diagnosed with endometrial cancer over age 60, however, it has been recommended that tumor studies to screen for Lynch syndrome be limited to patients age 60 or younger.

Additionally, researchers report the addition of a specific DNA-level test (known as tumor microsatellite instability typing or MSI) can increase Lynch syndrome detection rates among endometrial cancer patients by 12 percent.

As a result of this new data, researchers encourage Lynch syndrome testing in all newly diagnosed endometrial cancer patients – regardless of age – and the addition of a specific DNA-level test shown to improve detection rates.

“Limiting testing to patients age 60 or younger means 1 in 5 Lynch syndrome endometrial cancer patients would go unrecognized. The increased cancer risk for relatives of the Lynch endometrial cancer patients older than 60 would not be known or accounted for, so, the opportunity for early detection and intervention woud be lost. We believe that all endometrial cancer patients should have tumor analysis to screen of Lynch syndrome should be for, irrespective of age. The benefit of earlier detection of cancers and pre-cancers in mutation carriers is well established,” says Paul Goodfellow, PhD, corresponding author of the study.

Goodfellow and his colleagues reported their findings online ahead of print Nov. 9, 2015, in the Journal of Clinical Oncology.

“If we don’t identify patients who have these fundamental changes in their DNA structure then we also can’t use this information to help stop and detect these cancers in their at-risk relatives,” says Paul Goodfellow, who conducts research as part of The OSUCCC – James Molecular Biology and Cancer Genetics program.

Study Design and Results

In the current study, researchers sought to determine whether adding a certain type of MSI testing could improve Lynch syndrome detection rates above and beyond existing methods. The test helps oncologists identify and evaluate mutations that occur in small strands of DNA and can inform cancer risk.

Researchers analyzed matched tumor and normal tissue samples from more than 1000 endometrial cancer patients who participated in a National Cancer Institute cooperative group trial (GOG-210) now closed to patient accrual. Demographic information, cancer family history and specific tumor characteristics were also factored into the study analysis.

Results showed that that adding tumor DNA testing (microsatellite instability typing) significantly increased the number of Lynch syndrome mutations detected in endometrial cancer patients.

Age of diagnosis was younger for mutation carriers compared with non-carriers, but nearly one quarter of carriers were diagnosed over age 60.

The analysis suggested a possible mismatch repair mutation for nearly 12 percent of tumors and found that Lynch syndrome tumor screening which also includes microsatellite instability analysis can resulted in the detection of more germline mutation carriers. “These additional Lynch syndrome diagnoses would not be made if only tumor protein expression studies were performed,” says Goodfellow. “Having this knowledge about increased cancer risk could influence a patient’s care and surveillance decisions as well as change screening recommendations for family members.”

“By knowing who is at most risk for Lynch syndrome-related cancers, we have the potential to detect these devastating diagnoses in precancerous state through more intensive, targeted cancer surveillance. That knowledge and action is simply vital for relative of people with Lynch syndrome to reduce the risk of an advanced cancer diagnosis,” adds Goodfellow.

Research was supported with funding from the National Institutes of Health/NCI (grant CA134254), Barnes-Jewish Hospital and Siteman Cancer Center, The Ohio State University James Comprehensive Cancer Center and NCI Gynecologic Oncology Group and its subsidiaries (grants CA 27469, CA 37517, CA180822, CA27469, CA114793, and CA180868).

OSUCCC – James study collaborators include Heather Hampel MS, LGC, Floor Backes MD, Caroline Billingsley, David E. Cohn, MD, Nilsa Ramirez, Luke Simmons and Alexis S. Chassen. Collaborators from other institutions include, Amy P. Schmidt, Feng Gao, MD, Louise Brinton, MD, Lisa Landrum, MD, Melissa Geller, MD, Paul DiSilvestro, MD, Michael Pearl, MD, Shashikant Lele,MD, Matthew Powell, MD, Richard J. Zaino, MD and David Mutch MD.

About the OSUCCC – James

The Ohio State University Comprehensive Cancer Center – Arthur G. James Cancer Hospital and Richard J. Solove Research Institute strives to create a cancer-free world by integrating scientific research with excellence in education and patient-centered care, a strategy that leads to better methods of prevention, detection and treatment. Ohio State is one of only 45 National Cancer Institute-designated Comprehensive Cancer Centers and one of only four centers funded by the NCI to conduct both phase I and phase II clinical trials on novel anticancer drugs. As the cancer program’s 306-bed adult patient-care component, The James is one of the top cancer hospitals in the nation as ranked by U.S. News & World Report and has achieved Magnet designation, the highest honor an organization can receive for quality patient care and professional nursing practice. At 21 floors with more than 1.1 million square feet, The James is a transformational facility that fosters collaboration and integration of cancer research and clinical cancer care.

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