Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations

• Main Authors: Stefano Paolacci, Raul Ettore Mattassi, Giuseppe Marceddu, Elena Manara, Alessandra Zulian, Giulia Guerri, Luca De Antoni, Carlo Arduino, Daniela Cavalca, Matteo Bertelli
• Format: Article
• Language: English
• Published: MDPI AG 2020-10-01
• Series: Journal of Clinical Medicine
• Subjects: vascular malformations; next generation sequencing; tailored therapy
• Online Access: https://www.mdpi.com/2077-0383/9/11/3387

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 <i>PIK3CA</i> (18%, 21/115) and <i>TEK</i> (13/115, 11%). We also found mutations in <i>GNAQ</i>, <i>CCM2</i> and <i>PTEN</i>. 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.