ALK, NTRK1, NTRK2, NTRK3, or ROS1 gene fusions

High-grade gliomas with distinctive molecular characteristics arise in infants, typically in those diagnosed during the first year of life.[19-21] These tumors are characterized by recurrent oncogenic gene fusions involving ALK, NTRK1, NTRK2, NTRK3, or ROS1 as the primary and, typically, sole oncogenic driver. Infants with this type of glioma, now classified as infant-type hemispheric glioma, have a much better prognosis compared with older children with high-grade gliomas. Remarkably, these tumors may evolve from high-grade to low-grade histology over time, and it remains unclear how much this phenomenon is a consequence of natural disease history versus treatment-induced changes.[19]

ROS1 gene fusions have also been reported in gliomas occurring in older children and adults. A retrospective meta-analysis that included 40 children older than 1 year revealed that ROS1 gene fusions occurred in diverse glioma histologies, including diffuse high-grade and low-grade gliomas and glioneuronal tumors.[21] Similar to ROS1-altered cases occurring in infants, tumor variants in other known driver genes were rare. However, tumor copy number alterations were more frequent in older children than infants.