Journal article
Recurrent TRAK1::RAF1 Fusions in pediatric low‐grade gliomas
Brain pathology (Zurich, Switzerland), Vol.33(5), e13185
09/2023
DOI: 10.1111/bpa.13185
PMCID: PMC10467040
PMID: 37399073
Abstract
Fusions involving CRAF (RAF1) are infrequent oncogenic drivers in pediatric low-grade gliomas, rarely identified in tumors bearing features of pilocytic astrocytoma, and involving a limited number of known fusion partners. We describe recurrent TRAK1::RAF1 fusions, previously unreported in brain tumors, in three pediatric patients with low-grade glial-glioneuronal tumors. We present the associated clinical, histopathologic and molecular features. Patients were all female, aged 8 years, 15 months, and 10 months at diagnosis. All tumors were located in the cerebral hemispheres and predominantly cortical, with leptomeningeal involvement in 2/3 patients. Similar to previously described activating RAF1 fusions, the breakpoints in RAF1 all occurred 5′ of the kinase domain, while the breakpoints in the 3′ partner preserved the N-terminal kinesin-interacting domain and coiled-coil motifs of TRAK1. Two of the three cases demonstrated methylation profiles (v12.5) compatible with desmoplastic infantile ganglioglioma (DIG)/desmoplastic infantile astrocytoma (DIA) and have remained clinically stable and without disease progression/recurrence after resection. The remaining tumor was non-classifiable; with focal recurrence 14 months after initial resection; the patient remains symptom free and without further recurrence/progression (5 months post re-resection and 19 months from initial diagnosis). Our report expands the landscape of oncogenic RAF1 fusions in pediatric gliomas, which will help to further refine tumor classification and guide management of patients with these alterations.
Details
- Title: Subtitle
- Recurrent TRAK1::RAF1 Fusions in pediatric low‐grade gliomas
- Creators
- Jamal K. Benhamida - Memorial Sloan Kettering Cancer CenterHannah J. Harmsen - Vanderbilt University Medical CenterDeqin Ma - University of IowaChristopher M. William - NYU Langone HealthBryan K. Li - Memorial Sloan Kettering Cancer CenterLiliana Villafania - Memorial Sloan Kettering Cancer CenterPurvil Sukhadia - Memorial Sloan Kettering Cancer CenterKerry A. Mullaney - Memorial Sloan Kettering Cancer CenterMichael C. Dewan - Vanderbilt University Medical CenterEfsevia Vakiani - Memorial Sloan Kettering Cancer CenterMatthias A. Karajannis - Memorial Sloan Kettering Cancer CenterMatija Snuderl - NYU Langone HealthDavid Zagzag - NYU Langone HealthMarc Ladanyi - Memorial Sloan Kettering Cancer CenterMarc K. Rosenblum - Memorial Sloan Kettering Cancer CenterTejus A. Bale - Memorial Sloan Kettering Cancer Center
- Resource Type
- Journal article
- Publication Details
- Brain pathology (Zurich, Switzerland), Vol.33(5), e13185
- DOI
- 10.1111/bpa.13185
- PMID
- 37399073
- PMCID
- PMC10467040
- NLM abbreviation
- Brain Pathol
- ISSN
- 1015-6305
- eISSN
- 1750-3639
- Language
- English
- Electronic publication date
- 07/03/2023
- Date published
- 09/2023
- Academic Unit
- Pathology
- Record Identifier
- 9984442026002771
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