A novel tool for identifying the genetic changes in Lynch syndrome genes that are likely to be responsible for causing symptoms of the disease has been developed, calibrated and validated by an international team of researchers led by Huntsman Cancer Institute (HCI) at the University of Utah (U of U). The results were published this week in the journal Genetics in Medicine.
Millions of distinct changes are possible in genes that control health, and it is a massive undertaking to identify which specific changes are associated with developing disease. Some genetic changes are believed to have no impact at all, while others carry significant risk. Researchers at Huntsman Cancer Institute work to understand and classify which gene changes are likeliest to cause disease, as well as to identify appropriate strategies to help manage disease risk.
This groundbreaking study was led by Sean Tavtigian, PhD, a cancer researcher at HCI and professor of oncological sciences at the U of U. The work was built on a decade-long international collaboration. "Correctly identifying which of the genetic changes we observe actually result in disease is fundamentally important in clinical care," said Tavtigian. "Having clarity on this issue has the potential to add years to patients' lives, reduce anxiety about disease risk, and use health care dollars more efficiently."
"A key point is that we believe the accuracy of the tool combining the CIMRA test with the previously published computational analysis to be about 97 percent, making it appropriate for clinical use," said Tavtigian. de Wind added that the work "represents a new pinnacle in the classification of genetic variation."
The authors believe that routine utilization of their methods will dramatically increase the rate of risk classification for genetic changes that previously were poorly understood. Moreover, this calibration strategy provides a template for the development, validation, and calibration of reliable strategies for the diagnostic assessment of other hereditary cancer predisposition syndromes and genetic disorders.