ROS1 Alterations as a Potential Driver in Gliomas

ROS1 alterations are uncommon in gliomas and are primarily described in infants. In this episode, our host discusses with Dr. Xinyan Lu from the Feinberg School of Medicine in Chicago her team’s recent study on characterizing the clinicopathological features and molecular signatures of the full spectrum of ROS1 fusion–positive gliomas across all age groups. A multi-institutional cohort of 32 new and 58 published cases was divided into 3 age groups (19 infants, 40 pediatric patients, and 31 adults). Tumors in infants and adults showed uniformly high-grade morphology; however, tumors in pediatric patients exhibited diverse histologic features. The GOPC::ROS1 fusion was prevalent (61/79, 77%) across all age groups. Adult tumors showed recurrent genomic alterations characteristic of IDH wild-type glioblastoma, including the +7/-10/CDKN2A deletion and amplification of CDK4, MDM2, and PDGFRA. The outcomes were significantly poorer in adult patients.

The authors conclude that ROS1 likely acts as a driver in infant and pediatric gliomas and as a driver or codriver in adult gliomas. Integrated comprehensive clinical testing might be helpful in identifying such patients for possible targeted therapy.