Recurrent TRAK1::RAF1 fusions in pediatric low-grade gliomas Journal Article
| Authors: | Benhamida, J. K.; Harmsen, H. J.; Ma, D.; William, C. M.; Li, B. K.; Villafania, L.; Sukhadia, P.; Mullaney, K. A.; Dewan, M. C.; Vakiani, E.; Karajannis, M. A.; Snuderl, M.; Zagzag, D.; Ladanyi, M.; Rosenblum, M. K.; Bale, T. A. |
| Article Title: | Recurrent TRAK1::RAF1 fusions in pediatric low-grade gliomas |
| 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. © 2023 The Authors. Brain Pathology published by John Wiley & Sons Ltd on behalf of International Society of Neuropathology. |
| Keywords: | child; clinical article; human tissue; preschool child; school child; cancer surgery; unclassified drug; genetics; histopathology; microscopy; cancer recurrence; case report; raf protein; neuroimaging; brain tumor; follow up; glioma; brain neoplasms; protein domain; computer assisted tomography; brain cortex; pathology; retrospective study; dna methylation; childhood cancer; carcinogenesis; amino terminal sequence; infant; reoperation; gene fusion; craniotomy; seizure; frontal lobe; chromosome deletion; astrocytoma; white matter; brain edema; parietal lobe; vesicular transport adaptor protein; adaptor proteins, vesicular transport; chromosome 15q; hemisphere; low-grade gliomas; oncogene fusion; leptomeninx; ganglioglioma; tumor thickness; pilocytic astrocytoma; occipital lobe; craf; humans; brain pathology; human; female; article; omphalocele; happy puppet syndrome; raf1; pediatric patient; subcortex; t1 weighted imaging; glioneuronal tumors; oncogene fusion protein; trafficking kinesin protein 1; raf1 protein, human; trak1 protein, human; desmoplastic infantile astrocytoma; desmoplastic infantile ganglioglioma; prader willi syndrome |
| Journal Title: | Brain Pathology |
| Volume: | 33 |
| Issue: | 5 |
| ISSN: | 1015-6305 |
| Publisher: | Blackwell Publishing |
| Date Published: | 2023-09-01 |
| Start Page: | e13185 |
| Language: | English |
| DOI: | 10.1111/bpa.13185 |
| PUBMED: | 37399073 |
| PROVIDER: | scopus |
| PMCID: | PMC10467040 |
| DOI/URL: | |
| Notes: | The MSK Cancer Center Support Grant (P30 CA008748) is acknowledged in the PDF -- Corresponding author is MSK author: Tejus A. Bale -- Source: Scopus |
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MSK Authors
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141Karajannis -
424Rosenblum -
1328Ladanyi -
264Vakiani -
31Villafania -
28Sukhadia -
48Mullaney -
80Benhamida -
122Bale -
8Li
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