Posted: Tuesday, November 8, 2022
Findings presented in Acta Neuropathologica Communications suggest a key role to revealing the presence of druggable targets, including NTRK-driven tumors, when treating adolescent patients with spinal cord low-grade gliomas. The ability to characterize the complex molecular genetics of these particular gliomas was “invaluable” to refine a diagnosis and potentially lead to disease control with targeted therapy, concluded the pediatric neuro-oncologist Michal Zapotocky, MD, PhD, of Charles University and the University Hospital Motol, Prague, and colleagues.
To define the molecular landscape of these pediatric tumors of the central nervous system, the authors integrated clinical data, histology, and multilevel genetic and epigenetic analysis from a group of 26 pediatric patients with spinal cord tumors. The authors found a driver molecular alteration in 24 patients (92%). In four patients, a novel variant of KIAA1549::BRAF fusion was identified using RNA sequencing. Of note, the authors observed, only one-third of oncogenic drivers could be revealed using standard diagnostic methods, whereas the remaining patients with spinal cord low-grade gliomas required extensive molecular examination.
Nearly all the detected alterations (23 total) were potentially druggable targets, the authors said. Among the group, four patients received targeted therapy with MEK or TRK inhibitors. Although 55% of the tumors were clustered with pilocytic astrocytoma, other rare entities were identified in the patient population. In particular, the investigators found diffuse leptomeningeal glioneuronal tumors, high-grade astrocytoma with piloid features, and pleomorphic xanthoastrocytoma. Of the tumors detected, 14% had no match with the current version of the classifier.
“Comprehensive genomic analysis was critical not only to uncover the molecular landscape of pediatric spinal cord low-grade gliomas but also to identify high-priority targets for novel therapies,” the authors concluded.
Disclosure: The authors reported no conflicts of interest.