Recurrent TRAK1::RAF1 Fusions in pediatric low-grade gliomas.

Area of Science:

• Oncology
• Genetics
• Pediatric Neurosurgery

Background:

• RAF1 (CRAF) fusions are rare oncogenic drivers in pediatric low-grade gliomas.
• Known RAF1 fusion partners are limited, and they are infrequently found in pilocytic astrocytoma features.

Purpose of the Study:

• To describe novel TRAK1::RAF1 fusions in pediatric low-grade glial-glioneuronal tumors.
• To present the clinical, histopathologic, and molecular characteristics of these tumors.
• To expand the landscape of oncogenic RAF1 fusions in pediatric gliomas.

Main Methods:

• Case series analysis of three pediatric patients.
• Clinical data review.
• Histopathologic examination.
• Molecular analysis including gene fusion identification and DNA methylation profiling.

Main Results:

• Three pediatric patients (all female, aged 8 years, 15 months, and 10 months) presented with low-grade glial-glioneuronal tumors harboring TRAK1::RAF1 fusions.
• Tumors were primarily cortical in the cerebral hemispheres, with leptomeningeal involvement in two cases.
• Two tumors showed methylation profiles consistent with desmoplastic infantile ganglioglioma/astrocytoma and remained stable post-resection.
• One tumor recurred focally at 14 months but remained asymptomatic post-re-resection.

Conclusions:

• TRAK1::RAF1 fusions represent a novel class of oncogenic drivers in pediatric low-grade gliomas.
• These findings contribute to refining tumor classification and guiding clinical management strategies for affected children.
• The study highlights the importance of molecular profiling in identifying rare genetic alterations in pediatric brain tumors.