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NTRK2 gene fusions are uncommon in pilocytic astrocytoma

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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.

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Availability of data and material

The datasets used and/or analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

AGBL4 :

AGBL carboxypeptidase 4.

BAC :

Bacterial Artificial Chromosome.

BRAF :

B-Raf proto-oncogene, serine/threonine kinase.

CDKN2A/B :

Cyclin dependent kinase inhibitor 2 A/B.

CNS :

Central Nervous System Tumor.

dUTP :

2’-deoxyuridine 5’-triphosphate.

FDA :

Food and Drug Administration.

FGFR :

Fibroblast Growth Factor Receptor.

FISH :

Fluorescence In Situ Hybridization.

IDH :

Isocitrate Dehydrogenase.

KANK1 :

KN motif and ankyrin repeat domains 1.

KCTD16 :

Potassium channel tetramerization domain containing 16.

KCTD8 :

Potassium channel tetramerization domain containing 8.

KIF5B :

Kinesin family member 5B.

KRAS :

KRAS proto-oncogene, GTPase.

MAPK :

Mitogen-Activated Protein Kinase.

MTAP :

Methylthioadenosine phosphorylase.

NACC2 :

NACC (Nucleus accumbens associated) family member 2.

NF1 :

Neurofibromin 1.

NTRK :

Neurotrophic Tyrosine Receptor Kinase.

PCR :

Polymerase Chain Reaction.

PTPN11 :

Protein tyrosine phosphatase non-receptor type 11.

QKI :

KH domain containing RNA binding.

TMA :

Tissue microarrays.

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Acknowledgements

This study was partially supported by National Council for Scientific and Technological Development (CNPq), Brazil; São Paulo Foundation for Research Support (FAPESP), Brazil; Coordination for the Improvement of Level Personnel (CAPES), Brazil; The Cancer Center Support Grant (CCSG), USA.

Funding

National Council for Scientific and Technological Development (CNPq- 475358/2011-2) and São Paulo Foundation for Research Support (FAPESP − 2012/19590-0) grants to Rui Manuel Reis and the NIH-P30CA046934 (CCSG Molecular Pathology/Cytogenetics) to Marileila Varella-Garcia. Weder Menezes was a recipient of a Coordination for the Improvement of Level Personnel (CAPES, Brazil) fellowship.

Author information

Authors and Affiliations

  1. Molecular Oncology Research Center, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela St, 14784-400, Barretos, SP, Brazil

    Daniel Antunes Moreno, Weder Menezes & Rui Manuel Reis PhD

  2. James Cancer Hospital and Solove Research Institute Columbus, Ohio, USA

    Aline Paixão Becker

  3. Department of Pathology, Barretos Cancer Hospital, Barretos, São Paulo, Brazil

    Cristovam Scapulatempo-Neto

  4. University of Colorado School of Medicine, Aurora, CO, USA

    Jamie Sheren, Aline M Walter & Marileila Varella-Garcia

  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

    Jamie Sheren, Aline M Walter & Marileila Varella-Garcia

  6. Department of Neurosurgery, Barretos Cancer Hospital, 1331 Antenor Duarte Vilela St, 14784-400, Barretos, SP, Brazil

    Carlos Clara

  7. Department of Surgery, Ribeirao Preto, Brazil

    Hélio R. Machado & Ricardo S. Oliveira

  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

    Luciano Neder

  9. Life and Health Sciences Research Institute (ICVS), Medical School, University of Minho, Braga, Portugal

    Rui Manuel Reis PhD

  10. ICVS/3B’s - PT Government Associate Laboratory, Braga, Guimarães, Portugal

    Rui Manuel Reis PhD

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  1. Daniel Antunes Moreno
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Contributions

Daniel Antunes Moreno: Data analysis, results discussion, manuscript writing. Aline Paixão Becker: Data collection, experimental procedures, manuscript review. Cristovam Scapulatempo-Neto: Pathological review of tumor samples, manuscript review. Weder Menezes: Experimental procedures, data analysis. Jamie Sheren: experimental procedures, data analysis, manuscript review. Aline M Walter: experimental procedures, data analysis, manuscript review. Carlos Clara: Medial reports analysis, patients’ treatment protocol review. Hélio R. Machado: Medial reports analysis, selection of patients for the study. Ricardo S. Oliveira: Medial reports analysis, selection of patients for the study. Luciano Neder: Pathological review of tumor samples and manuscript review. Marileila Varella-Garcia: experimental procedures, data analysis, manuscript review. Rui Manuel Reis: Supervisor and project coordinator, results discussion, manuscript review and writing.

Corresponding author

Correspondence to Rui Manuel Reis PhD.

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Ethical standards

The study was approved by local Ethics Committee of Barretos Cancer Hospital, Barretos (number HCB/87362), and Ribeirão Preto Medical School, University of São Paulo, Brazil (HCRP/212313) and is in accordance with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.

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The authors declare that they have no competing interests.

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Moreno, D.A., Becker, A.P., Scapulatempo-Neto, C. et al. NTRK2 gene fusions are uncommon in pilocytic astrocytoma. Mol Biol Rep 49, 7567–7573 (2022). https://doi.org/10.1007/s11033-022-07567-y

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