Liquid Biopsies for the Detection of Somatic Mutations in bAVMs

"Personalized medicine has revolutionized patient care, particularly in oncology. Brain arteriovenous malformations (bAVMs) are abnormal vessels located on the surface of the brain or within the brain parenchyma, causing abnormal communication between arterial and venous networks, without the interposition of the capillary bed. The main risk of these malformations is rupture, leading to intracranial bleeding, which can cause severe sequelae or even death. bAVMs (except those of clearly identified genetic origin \[\< 5%\], such as mutations associated with Rendu-Osler disease) have long been considered non-genetic in origin.

However, somatic genetic mutations activating the RAS/RAF/MEK/ERK (MAPK) signaling pathway have recently been identified in surgical specimens of bAVMs. Additionally, targeted inhibition of this pathway is effective in treating these malformations in animals and appears to be effective in extracranial arteriovenous malformations, particularly superficial ones.

Next-generation sequencing of circulating DNA on liquid biopsies is a promising and minimally invasive approach to studying the presence of mutations in arteriovenous malformations.

The treatment of a bAVM aims to obliterate the malformation to prevent or avoid the risk of hemorrhage. It may involve several therapeutic modalities: microsurgery, endovascular embolization, and radiosurgery. These treatments can be combined, and microsurgery is often preceded by pre-surgical embolization, aimed at reducing the hemorrhagic risk of the intervention. However, these are invasive treatments, not without risk.

The identification of mutations through liquid biopsies could enable the development of non-invasive targeted therapies against these bAVMs.

This research aims to identify somatic genetic mutations activating the MAPK signaling pathway in bAVMs. These mutations have already been identified in surgical specimens. This research aims to evaluate the diagnostic performances of liquid biopsies (detection of genetic mutations in blood samples, i.e., circulating DNA), with the gold standard being the detection of the same mutations in surgical specimens."