Integrated molecular and clinical analysis of BRAF-mutant glioma in adults

Karisa C Schreck; Pinky Langat; Varun M Bhave; Taibo Li; Eleanor Woodward; Christine A Pratilas; Charles G Eberhart; Wenya Linda Bi

doi:10.1038/s41698-023-00359-y

Integrated molecular and clinical analysis of BRAF-mutant glioma in adults

NPJ Precis Oncol. 2023 Feb 28;7(1):23. doi: 10.1038/s41698-023-00359-y.

Authors

Karisa C Schreck^#^{1

2}, Pinky Langat^#³, Varun M Bhave³, Taibo Li⁴, Eleanor Woodward³, Christine A Pratilas^{5

6}, Charles G Eberhart^{5

7}, Wenya Linda Bi^{8

9}

Affiliations

¹ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ksolt1@jhmi.edu.
² Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA. ksolt1@jhmi.edu.
³ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA.
⁴ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁵ Department of Oncology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁶ Department of Pediatrics, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁷ Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD, USA.
⁸ Department of Neurosurgery, Brigham and Women's Hospital, Harvard Medical School, Boston, MA, USA. wbi@bwh.harvard.edu.
⁹ Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, USA. wbi@bwh.harvard.edu.

^# Contributed equally.

Abstract

BRAF mutations are a significant driver of disease in pediatric low-grade glioma, but the implications of BRAF alterations on the clinical course and treatment response in adult glioma remain unclear. Here, we characterize a multi-institutional cohort of more than 300 patients (>200 adults) with BRAF-mutated glioma using clinical, pathological/molecular, and outcome data. We observed that adult and pediatric BRAF-mutant gliomas harbor distinct clinical and molecular features, with a higher prevalence of BRAF^V600E (Class I) and BRAF fusions in pediatric tumors. BRAF^V600E alterations were associated with improved survival in adults with glioma overall, though not in glioblastoma. Other genomic alterations observed within functional classes were consistent with the putative roles of those BRAF mutation classes in glioma pathogenesis. In our adult cohort, BRAF^V600E alterations conferred sensitivity to targeted therapies. Overall, this large cohort of BRAF-altered adult gliomas demonstrates a broad range of molecular alterations with implications for treatment sensitivity and survival.