Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations.
Stefano PaolacciRaul Ettore MattassiGiuseppe MarcedduElena ManaraAlessandra ZulianGiulia GuerriLuca De AntoniCarlo ArduinoDaniela CavalcaMatteo BertelliPublished in: Journal of clinical medicine (2020)
Vascular malformations include various disorders characterized by morphological, structural and/or functional alterations of blood and lymph vessels. Most are sporadic, due to somatic mutations. Here, we report a cohort of patients with sporadic and/or unifocal vascular malformations, in whom we carried out next generation sequencing analysis of a panel of genes associated with vascular malformations. The 115 patients analyzed were from different clinical centres. In 37 patients (32%), we found pathogenic mutations: most of these were gain-of-function mutations in PIK3CA (18%, 21/115) and TEK (13/115, 11%). We also found mutations in GNAQ, CCM2 and PTEN. Identifying pathogenic variants in patients with vascular malformations can help improve management, particularly in cases with activating mutations that cause an increase in cell proliferation. Personalized pharmacological treatment, if possible, is now considered preferable to surgery and can help prevent recurrences, i.e., long-term complications of residual malformation or regrowth of tumors. For instance, rapamycin is currently being investigated for the treatment of various vascular malformations associated with hyperactivation of the phosphoinositide 3-kinase/Akt/mammalian target of rapamycin (PI3K/Akt/mTOR) pathway.
Keyphrases
- cell proliferation
- end stage renal disease
- ejection fraction
- chronic kidney disease
- newly diagnosed
- copy number
- signaling pathway
- peritoneal dialysis
- coronary artery disease
- high resolution
- dna methylation
- amyotrophic lateral sclerosis
- pi k akt
- tyrosine kinase
- combination therapy
- atomic force microscopy
- circulating tumor