Somatic mutations in intracranial arteriovenous malformations

Area of Science:

• Neuroscience
• Genetics
• Oncology

Background:

• Intracranial arteriovenous malformation (AVM) is a significant cause of primary intracerebral hemorrhage in young adults.
• AVM lesions are typically sporadic and often harbor somatic mutations in KRAS or BRAF genes.

Purpose of the Study:

• To identify somatic mutations in a cohort of patients with brain AVM.
• To investigate potential genotype-phenotype associations in intracranial AVM.

Main Methods:

• Multiplex targeted sequencing (MIP-seq) was performed on 16 human brain AVM specimens.
• Droplet digital PCR (ddPCR) was used for mutation confirmation and screening.
• Patient and AVM characteristics were systematically recorded.

Main Results:

• Somatic mutations were detected in 63% (10 of 16) of AVM specimens.
• KRAS mutations (G12D, G12V) were found in eight specimens, and BRAF mutations (V600E, Q636X) in two.
• No significant differences in clinical or demographic features were observed between mutated and non-mutated AVMs, or between KRAS and BRAF mutation groups, although two BRAF cases presented at an older age.

Conclusions:

• Somatic mutations in KRAS and BRAF are common in intracranial AVMs but not universally present.
• Currently, no clear genotype-phenotype correlations exist to predict mutation presence or type in AVMs.