KRAS/BRAF mutations in brain arteriovenous malformations: A systematic review and meta-analysis

Abstract

Introduction Somatic KRAS mutations have been identified in the majority of brain arteriovenous malformations (AVM) specimens. The aim of our study was to evaluate the prevalence of Kirsten rat sarcoma (KRAS)/murine sarcoma viral oncogene homolog B1 (BRAF) mutations in brain AVM. Methods A systematic literature review was performed in November 2019. We reviewed MEDLINE/PubMed, Cochrane Library, and ClinicalTrials.gov for citation or ongoing trials from January 2010 to March 2020. Results 6 studies were identified as meeting the inclusion criteria of this review. The total frequency of KRAS mutations in 1726 patients with AVM was 55%. The prevalence of BRAF mutation was 7.5%. The prevalence of AVMs with grade 2 was the most (39%). Frontal and parietal lobes were the commonest sites of AVMs (21%). the most prevalent presentation of patients with AVM was hemorrhage (62%). Conclusion Our findings support a high prevalence of somatic activating mutations in KRAS and less commonly, BRAF in the overwhelming majority of brain AVMs. Practically and importantly, this pathway homogeneity in CNS arteriovenous malformations also supports the development of targeted therapies with RAS/RAF pathway inhibitors. However, more studies are needed to confirm this hypothesis.