MET somatic activating mutations are responsible for lymphovenous malformation and can be identified using cell-free DNA next generation sequencing liquid biopsy.

摘要: Abstract Objective Germline mutations of either the endothelial cell-specific tyrosine kinase receptor TIE2 or glomulin (GLMN) gene are responsible for rare inherited venous malformations. Both genes affect hepatocyte growth factor c-Met, inducing vascular smooth muscle cell migration. lymphatic malformations, leading to lymphedema. The molecular alteration abnormal mixed anomaly defined as lymphovenous malformation has remained unknown. Methods A group 4 patients with malformations were selected. Plasma was obtained from both peripheral and efferent vein samples at site cell-free DNA extraction. When possible, we analyzed tissue biopsy lesion. Results We have demonstrated that in all four patients, an activating MET mutation present. In three same pathogenic mutation, T1010I, identified. found level patient available, confirming its causative role Conclusions present study, next generation sequencing liquid is able identify affected tissues. Although a wider cohort necessary confirm these data suggest could result postzygotic somatic key regulators development. noninvasiveness method avoids any risk bleeding can be easily performed children. confident pioneering results provided viable alternative future diagnosis, allowing subsequent therapy tailored genetic defect.