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MET somatic activating mutations are responsible for lymphovenous malformation and can be identified using cell-free DNA next generation sequencing liquid biopsy.
- Source :
-
Journal of vascular surgery. Venous and lymphatic disorders [J Vasc Surg Venous Lymphat Disord] 2021 May; Vol. 9 (3), pp. 740-744. Date of Electronic Publication: 2020 Aug 26. - Publication Year :
- 2021
-
Abstract
- Objective: Germline mutations of either the endothelial cell-specific tyrosine kinase receptor TIE2 or the glomulin (GLMN) gene are responsible for rare inherited venous malformations. Both genes affect the hepatocyte growth factor receptor c-Met, inducing vascular smooth muscle cell migration. Germline mutations of hepatocyte growth factor are responsible for lymphatic malformations, leading to lymphedema. The molecular alteration leading to the abnormal mixed vascular anomaly defined as lymphovenous malformation has remained unknown.<br />Methods: A group of 4 patients with lymphovenous malformations were selected. Plasma was obtained from both peripheral and efferent vein samples at the vascular malformation site for cell-free DNA extraction. When possible, we analyzed tissue biopsy samples from the vascular lesion.<br />Results: We have demonstrated that in all four patients, an activating MET mutation was present. In three of the four patients, the same pathogenic activating mutation, T1010I, was identified. The mutation was found at the tissue level for the patient with tissue samples available, confirming its causative role in the lymphovenous malformations.<br />Conclusions: In the present study, we have demonstrated that cell-free DNA next generation sequencing liquid biopsy is able to identify the MET mutations in affected tissues. Although a wider cohort of patients is necessary to confirm its causative role in lymphovenous malformations, these data suggest that lymphovenous malformations could result from postzygotic somatic mutations in genes that are key regulators of lymphatic development. The noninvasiveness of the method avoids any risk of bleeding and can be easily performed in children. We are confident that the present pioneering results have provided a viable alternative in the future for lymphovenous malformation diagnosis, allowing for subsequent therapy tailored to the genetic defect.<br /> (Copyright © 2020 Society for Vascular Surgery. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- Adult
Cell-Free Nucleic Acids blood
Female
Genetic Association Studies
Genetic Predisposition to Disease
Humans
Italy
Liquid Biopsy
Lymphatic Abnormalities diagnostic imaging
Male
Middle Aged
Phenotype
Predictive Value of Tests
Prospective Studies
Proto-Oncogene Proteins c-met blood
Risk Assessment
Risk Factors
Vascular Malformations diagnostic imaging
Cell-Free Nucleic Acids genetics
DNA Mutational Analysis
High-Throughput Nucleotide Sequencing
Lymphatic Abnormalities genetics
Mutation
Proto-Oncogene Proteins c-met genetics
Vascular Malformations genetics
Subjects
Details
- Language :
- English
- ISSN :
- 2213-3348
- Volume :
- 9
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- Journal of vascular surgery. Venous and lymphatic disorders
- Publication Type :
- Academic Journal
- Accession number :
- 32858245
- Full Text :
- https://doi.org/10.1016/j.jvsv.2020.07.015