Dr. Burns on Identifying Genetic Alterations in Lung Cancer

Timothy F. Burns, MD, PhD, assistant professor of medicine, Department of Medicine, Division of Hematology/Oncology, at the University of Pittsburgh Cancer Institute, and medical oncologist at University of Pittsburgh Medical Center Hillman Cancer Center, discusses methods of identifying genetic alterations in lung cancer.

There are several ways to identify a translocation, but a tumor biopsy is the gold standard. For ALK, approaches include immunohistochemistry, fluorescence in situ hybridization (FISH), and next-generation sequencing (NGS). For ROS1, there is FISH and NGS, says Burns. If adequate tissue can’t be collected, blood-based testing is recommended. Standard blood-based testing with Guardant360 or FoundationOne sequences the DNA in the blood, but it also does fusion capture. However, fusion capture can be inaccurate, says Burns, and although a blood-based test can identify an ALK or ROS1 mutation, it may miss the fusion.

If a patient has a known ALK or ROS1 translocation that is missed on a blood-based assay, it is simply a failure of the fusion capture, says Burns. Therefore, blood-based assays have to be interpreted with caution. When it comes to sequencing the ALK or ROS1 gene for second-site mutations, both tissue-based and blood-based assays can be used to identify the right treatment for patients, concludes Burns.