ANALYSIS OF SOMATIC KRAS MUTATIONS IN PATIENTSDIAGNOSED WITH ARTERIOVENOUS MALFORMATIONSOF THE BRAIN

Abstract

Introduction. Cerebral arteriovenous malformations (AVMs) consist of abnormal tangles of dilated vascular structure
that connect arteries and veins directly without intermediate capillary layers. Most cerebral AVMs are presumably sporadic;
however, rare familial cases occur. Brain AVMs pose a high risk of intracranial hemorrhages, which are significant causes of
morbidity and mortality from AVMs, especially in children and young adults. The pathogenesis of the sporadic form of AVM
remains poorly understood to this day.
Objective: Detection of Kirsten rat sarcoma (KRAS) mutations in brain AMB tissues using digital PCR.

Materials and methods: Genomic DNA was isolated from tissue samples using a commercial DNeasy Blood & Tissue
Kit, Qiagen according to the manufacturer's instructions. The DNA concentration was measured on a Qubit2 fluorimeter.
KRAS mutation detection was performed using a commercial PrimePCR™ ddPCR™ Mutation Detection Assay Kit, Bio-Rad
on a QX200 Droplet Digital PCR System, Bio-Rad. QuantaSoftTM Analysis Software (Bio-Rad) was used to interpret the
results.
Results: KRAS gene mutations were screened in tissues from patients with cerebral AVMs (n=8) by digital droplet PCR.
An activating mutation in the KRAS gene was detected in one of the eight samples examined (12.5%).
Conclusion: The presence of the mutation supports the possibility of a causal role of somatic mutations with the
formation of AVMs of the brain.