Abstract 402: High Prevalence Of Ras/mapk Pathway Mutations In Cell-free Dna Of Extracranial Arteriovenous Malformation: A New Method To Detect The Genotype

Abstract

Purpose: Extracranial Arteriovenous Malformations(AVMs) were primarily caused by somatic mutations in KRAS and MAP2K1 genes. Targeted chemotherapies are emerging but require molecular diagnosis. Since the AVMs were high flow and high pressure. It is hard to acquire the AVM lesion tissue where the mutant variants were only detected in. Few were detected in Cell-free DNA(CfDNA). Since absolute ethanol embolism is one of the effective methods for treating AVM. We hypothesized that CfDNA of post-embolism could provide the genotype of patients with AVMs. Methods: Peripheral Blood, lesion tissue specimens under the guidance of digital subtraction angiography(DSA), CfDNAs isolated from plasma of 40 patients underwent interventional embolism(before and after as T1(1h, setting first injecting ethanol moment as T0 )). 4 patients ‘s CfDNAs were collaborated in 8h(T8), 16h(T16), 24h(T24), 48h(T48), and 72h(T72) after T0. All the specimen were sequenced by a targeted NGS panel of vascular anomalies Results: Variants were detected in tissue and CfDNA but none in peripheral blood. The prevalence for tissue, CfDNA of pre-embolism and post-embolism(1h) were 73%(27/37), 27.5%(11/40), and 90%(36/40), respectively. KRAS(p.Gln61, p.Gly12) and MAP2K1(p.Gln56, p.Lys57) were the mutant hot spots. Novel mutations in BRAF, RASA1, KRAS, and MAP2K1 were also detected in tissue and cfDNA. As for specificity, area under the ROC curve were 0.8125(P<0.0001), 0.6375(P=0.0343), and 0.9500(P<0.0001). For the variants allele frequency(VAF) of CfDNA, the VAF reached a surge at T1, then a second surge at T24. Conclusion: AVMs were caused by mutations in RAS/MAPK pathway where cfDNA of post-embolism(T1) of absolute ethanol interventional therapy could provide the accurate genotype of the patients in sensitivity and specificity. VAF detected in T24 could provide information related to the natural metabolism such as the indications or prognosis of targeted chemotherapy. Overall, CfDNA of post-embolism provides us a new method for approaching the precise medicine of AVM.