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Additional genetic alterations in BRAF-mutant gliomas correlate with histologic diagnoses

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Abstract

Introduction

Recently, the term “Diffuse glioma, BRAF V600E-mutant” has been recommended for IDH-wildtype gliomas with BRAF p.V600E mutation and without CDKN2A/B deletion. However, additional alterations in gliomas that coexist with BRAF-mutations are poorly defined.

Methods

We analyzed next-generation sequencing results in 315 cancer-associated genes for 372 gliomas from our institution (2010 to 2017). In addition, we reviewed IDH-WT gliomas with mutation and copy-number alterations available in cBioPortal, to further characterize BRAF-mutant gliomas.

Results

Seventeen (4.6%) showed BRAF mutations. Tumor types included 8 glioblastomas, 2 epithelioid glioblastomas (E-GBM), 2 pleomorphic xanthoastrocytomas (PXA), 1 anaplastic oligodendroglioma, 1 diffuse astrocytoma, and 3 pilocytic astrocytomas. Fifty-three percent (53%) of cases exhibited BRAF-alterations other than p.V600E. The majority of the tumors were localized in the temporal lobe (52.9%). In addition to BRAF mutations, glioblastomas showed concomitant mutations in TP53 (3/8), CDKN2A/B-loss (6/8), TERT-promoter (6/8), and/or PTEN (5/8). Both E-GBMs and PXAs showed CDKN2A/B-loss and BRAF p.V600E with absence of TERTp, TP53, and PTEN mutations. Similar findings were observed in BRAF-mutant infiltrating gliomas from cBioPortal.

Conclusions

Knowledge of additional alterations that co-occur with BRAF-mutations in gliomas may improve diagnosis and help identify patients that could benefit from targeted therapies. Furthermore, we provide examples of two patients whose tumors responded to BRAF pathway inhibitors, arguing in favor of these therapies in patients with BRAF-mutant gliomas.

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Data availability

The datasets generated during and/or analyzed during the current study are available upon reasonable request to the corresponding authors.

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Acknowledgements

We would like to thank Melissa Stephens, Ayna Matyakuba, and Kimberly Fontenot for their assistance with this project.

Funding

Research reported in this publication was supported by the National Cancer Institute of the National Institutes of Health under Award Number K08CA241651 (LYB). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health.

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Authors and Affiliations

  1. Department of Pathology and Laboratory Medicine, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Antonio Dono, Jennifer Vu, Gabriella Hines, Takeshi Takayasu, Meenakshi B. Bhattacharjee & Leomar Y. Ballester

  2. Vivian L. Smith Department of Neurosurgery, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Antonio Dono, Molly Anapolsky, Yuanqing Yan, Nitin Tandon, Jay-Jiguang Zhu, Yoshua Esquenazi & Leomar Y. Ballester

  3. Memorial Hermann Hospital-TMC, Houston, TX, USA

    Nitin Tandon, Jay-Jiguang Zhu, Meenakshi B. Bhattacharjee, Yoshua Esquenazi & Leomar Y. Ballester

  4. Center for Precision Health, School of Biomedical Informatics, The University of Texas Health Science Center at Houston, Houston, TX, USA

    Yoshua Esquenazi

  5. Department of Pathology and Laboratory Medicine, Department of Neurosurgery, McGovern Medical School, UT Neuroscience, University of Texas Health Science Center at Houston, 6431 Fannin St., MSB 2.136, Houston, TX, 77030, USA

    Yoshua Esquenazi

  6. Vivian L. Smith Department of Neurosurgery and Center for Precision Health, UT-Neuroscience, McGovern Medical School, The University of Texas Health Science Center at Houston, 6400 Fannin Street, Suite # 2800, Houston, TX, 77030, USA

    Leomar Y. Ballester

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  1. Antonio Dono
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  2. Jennifer Vu
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Contributions

Experimental design: YE, LYB. Collection and assembly of data: AD, JV, MA, GH, TT, JJZ. Analysis and interpretation of the data: AD, JV, MA, GH, YY, YE, LYB. Manuscript writing: AD, JV, MA, GH, NT, YE, LYB. Final approval of manuscript: all authors.

Corresponding authors

Correspondence to Yoshua Esquenazi or Leomar Y. Ballester.

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The authors declared no conflict of interest.

Ethical approval

This retrospective study was approved by the institutional review board of The University of Texas Health Science Center at Houston and Memorial Hermann Hospital, Houston, TX, following the 1964 Helsinki Declaration and its later amendments.

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Dono, A., Vu, J., Anapolsky, M. et al. Additional genetic alterations in BRAF-mutant gliomas correlate with histologic diagnoses. J Neurooncol 149, 463–472 (2020). https://doi.org/10.1007/s11060-020-03634-1

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