Daniel Antunes Moreno1, Aline Paixão Becker2, Cristovam Scapulatempo-Neto3, Weder Menezes1, Jamie Sheren4,5, Aline M Walter4,5, Carlos Clara6, Hélio R Machado7, Ricardo S Oliveira7, Luciano Neder8, Marileila Varella-Garcia4,5, Rui Manuel Reis9,10,11. 1. Molecular Oncology Research Center, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela St, 14784-400, Barretos, SP, Brazil. 2. James Cancer Hospital and Solove Research Institute Columbus, Ohio, USA. 3. Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil. 4. University of Colorado School of Medicine, Aurora, CO, USA. 5. Department of Pathology, Colorado Molecular Correlates Laboratory (CMOCO), Molecular Pathology Shared Resource, Cytogenetics - Anschutz Medical Campus - RC1-South, Rm L18-8401A 12801 E 17th Ave, 80045, Aurora, CO, USA. 6. Department of Neurosurgery, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela St, 14784-400, Barretos, SP, Brazil. 7. Department of Surgery, Ribeirao Preto, Brazil. 8. Department of Pathology of Ribeirão Preto Medical School, University of São Paulo (FMRP-USP) - Campus of University of Sao Paulo, 14049-900, Ribeirao Preto, SP, Brazil. 9. Molecular Oncology Research Center, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela St, 14784-400, Barretos, SP, Brazil. ruireis.hcb@gmail.com. 10. Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal. ruireis.hcb@gmail.com. 11. ICVS/3B's - PT Government Associate Laboratory, Braga, Guimarães, Portugal. ruireis.hcb@gmail.com.
Abstract
BACKGROUND: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. METHODS: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. RESULTS: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. CONCLUSIONS: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features.
BACKGROUND: Pilocytic astrocytoma is the most frequent pediatric glioma. Despite its overall good prognosis, complete surgical resection is sometimes unfeasible, especially for patients with deep-seated tumors. For these patients, the identification of targetable genetic alterations such as NTRK fusions, raised as a new hope for therapy. The presence of gene fusions involving NTRK2 has been rarely reported in pilocytic astrocytoma. The aim of the present study was to investigate the frequency of NTRK2 alterations in a series of Brazilian pilocytic astrocytomas. METHODS: Sixty-nine pilocytic astrocytomas, previously characterized for BRAF and FGFR1 alterations were evaluated. The analysis of NTRK2 alterations was performed using a dual color break apart fluorescence in situ hybridization (FISH) assay. RESULTS: NTRK2 fusions were successfully evaluated by FISH in 62 of the 69 cases. Neither evidence of NTRK2 gene rearrangements nor NTRK2 copy number alterations were found. CONCLUSIONS: NTRK2 alterations are uncommon genetic events in pilocytic astrocytomas, regardless of patients' clinicopathological and molecular features.
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