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Clinical Characteristics of BRAF V600E Gene Mutation in Patients of Epilepsy-Associated Brain Tumor: a Meta-analysis

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Abstract

Epilepsy-associated brain tumors (EATs) are usually slow-growing, with seizures as the primary and most dominant symptom. BRAF (v-raf murine sarcoma viral oncogene homolog B1) gene mutations have been found in several subsets of EATs; the V600E mutation is currently believed to contribute to the intrinsic epileptogenicity and tumor growth. However, the relationship between BRAF V600E gene mutation and clinical characteristics in EAT patients is not clear. In this study, we aimed to systematically review the frequency of BRAF V600E gene mutation, as well as the relationship between BRAF V600E gene mutation and clinical characteristics, which may help with the diagnosis and treatment of EATs. Cochrane Library, PubMed, Embase, CNKI, WanFang Data, CQVIP, and SinoMed databases were searched up to October 2020 to identify peer-reviewed human studies on assessing the relationship between BRAF V600E gene mutations and clinical characteristics in EATs. The following data were calculated: the frequency of BRAF V600E mutation and clinical feature comparison between BRAF V600E mutations and wild type in EATs, such as gender, age of seizure onset, duration of epilepsy, location of tumors, and Engel outcome. A total of 12 articles were included in the analysis. Five hundred and nine patients with epilepsy-associated brain tumors were screened for the BRAF V600E gene mutation. Among them, 193 patients had the BRAF V600E mutation (34.06%, 95% CI = 0.25 to 0.43). The subgroup analyses of BRAF V600E mutation showed positive frequency of 44.76% (95% CI = 0.36 to 0.54) in ganglioglioma, 24.75% (95% CI = 0.14 to 0.37) in gysembryoplastic neuroepithelial tumor, 2.15% (95% CI = 0 to 0.19) in angiocentric glioma, and 50.16% (95% CI = 0.33 to 0.68) in pleomorphic xanthoastrocytoma. Compared with the overall frequency, the BRAF V600E positive frequency in ganglioglioma was significantly higher (P = 0.0283). We also found that BRAF V600E gene mutation was significantly associated with age at seizure onset (MD = −2.37; 95% CI = −4.33 to −0.41; P = 0.02). There was no statistical difference between BRAF V600E mutations and wild type in gender, duration of epilepsy, tumor site, and Engel outcome comparison. In conclusion, our updated and comprehensive meta-analysis based on a large number of clinical data demonstrated that BRAF V600E mutation is a specific biomarker and could be a pharmacological target for ganglioglioma patients and an exclusion diagnostic criterion for angiocentric glioma. This meta-analysis suggested the critical role of BRAF V600E mutation in the occurrence and development of EATs. Our findings help to elucidate the progression mechanisms in EATs and develop future therapeutic strategies for EATs.

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Data Availability

The datasets analyzed in this study are available from the corresponding author on request.

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Authors and Affiliations

  1. Department of Surgery, Rhode Island Hospital, Alpert Medical School of Brown University, Providence, RI, 02903, USA

    Hang Xing & Zhiqi Zhang

  2. Department of Ultrasound, First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan, 450052, China

    Yi Song

  3. Center for Systems Biology, Massachusetts General Hospital, 185 Cambridge Street, CPZN 5206, Boston, MA, 02114, USA

    Peter David Koch

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  1. Hang Xing
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  2. Yi Song
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  3. Zhiqi Zhang
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  4. Peter David Koch
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Contributions

Hang Xing and Yi Song designed the study. Hang Xing, Yi Song, and Zhiqi Zhang contributed to acquired, collected, and extracted data included in our meta-analysis. Hang Xing and Peter Koch performed the analysis work. Hang Xing drafted the manuscript. Yi Song, Peter Koch, and Zhiqi Zhang edited the manuscript. Peter Koch and Yi Song revised the manuscript. All authors read and approved the final manuscript.

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Correspondence to Yi Song.

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Xing, H., Song, Y., Zhang, Z. et al. Clinical Characteristics of BRAF V600E Gene Mutation in Patients of Epilepsy-Associated Brain Tumor: a Meta-analysis. J Mol Neurosci 71, 1815–1824 (2021). https://doi.org/10.1007/s12031-021-01837-3

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  • DOI: https://doi.org/10.1007/s12031-021-01837-3

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