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

Autor: Benhamida JK; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Harmsen HJ; Department of Pathology, Microbiology and Immunology, Vanderbilt University Medical Center, Nashville, Tennessee, USA., Ma D; Department of Pathology, University of Iowa Hospitals and Clinics, Iowa City, Iowa, USA., William CM; Department of Pathology, NYU Langone Health, New York, New York, USA., Li BK; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Villafania L; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Sukhadia P; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Mullaney KA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Dewan MC; Department of Neurological Surgery, Vanderbilt University Medical Center., Vakiani E; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Karajannis MA; Department of Pediatrics, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Snuderl M; Department of Pathology, NYU Langone Health, New York, New York, USA., Zagzag D; Department of Pathology, NYU Langone Health, New York, New York, USA.; Department of Neurosurgery, NYU Langone Health, New York, New York, USA., Ladanyi M; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.; Human Oncology and Pathogenesis Program, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Rosenblum MK; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA., Bale TA; Department of Pathology and Laboratory Medicine, Memorial Sloan Kettering Cancer Center, New York, New York, USA.
Jazyk: angličtina
Zdroj: Brain pathology (Zurich, Switzerland) [Brain Pathol] 2023 Sep; Vol. 33 (5), pp. e13185. Date of Electronic Publication: 2023 Jul 03.
DOI: 10.1111/bpa.13185
Abstrakt: 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.
(© 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology.)
Databáze: MEDLINE
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