Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations
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 car...
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doaj-bf9d6ab2b53745d4b79c026722c855032020-11-25T03:05:58ZengMDPI AGJournal of Clinical Medicine2077-03832020-10-0193387338710.3390/jcm9113387Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular MalformationsStefano Paolacci0Raul Ettore Mattassi1Giuseppe Marceddu2Elena Manara3Alessandra Zulian4Giulia Guerri5Luca De Antoni6Carlo Arduino7Daniela Cavalca8Matteo Bertelli9MAGI’S LAB, Via delle Maioliche, 57/D, 38068 Rovereto, TN, ItalyCenter for Vascular Malformations “Stefan Belov”, Clinical Institute Humanitas “Mater Domini”, Via Gerenzano, 2, 21053 Castellanza, VA, ItalyMAGI EUREGIO, Via Maso della Pieve, 60/A, 39100 Bolzano, ItalyMAGI EUREGIO, Via Maso della Pieve, 60/A, 39100 Bolzano, ItalyMAGI’S LAB, Via delle Maioliche, 57/D, 38068 Rovereto, TN, ItalyMAGI’S LAB, Via delle Maioliche, 57/D, 38068 Rovereto, TN, ItalyMAGI EUREGIO, Via Maso della Pieve, 60/A, 39100 Bolzano, ItalyMedical Genetics Unit, City of Health and Science, Corso Bramante, 88, 10126 Turin, ItalyLaser Surgery Operating Unit, Plastic Surgery Department, San Rocco Clinical Institute, Via dei Sabbioni, 24, 25050 Ome, BS, ItalyMAGI’S LAB, Via delle Maioliche, 57/D, 38068 Rovereto, TN, ItalyVascular 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.https://www.mdpi.com/2077-0383/9/11/3387vascular malformationsnext generation sequencingtailored therapy |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Stefano Paolacci Raul Ettore Mattassi Giuseppe Marceddu Elena Manara Alessandra Zulian Giulia Guerri Luca De Antoni Carlo Arduino Daniela Cavalca Matteo Bertelli |
spellingShingle |
Stefano Paolacci Raul Ettore Mattassi Giuseppe Marceddu Elena Manara Alessandra Zulian Giulia Guerri Luca De Antoni Carlo Arduino Daniela Cavalca Matteo Bertelli Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations Journal of Clinical Medicine vascular malformations next generation sequencing tailored therapy |
author_facet |
Stefano Paolacci Raul Ettore Mattassi Giuseppe Marceddu Elena Manara Alessandra Zulian Giulia Guerri Luca De Antoni Carlo Arduino Daniela Cavalca Matteo Bertelli |
author_sort |
Stefano Paolacci |
title |
Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations |
title_short |
Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations |
title_full |
Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations |
title_fullStr |
Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations |
title_full_unstemmed |
Somatic Variant Analysis Identifies Targets for Tailored Therapies in Patients with Vascular Malformations |
title_sort |
somatic variant analysis identifies targets for tailored therapies in patients with vascular malformations |
publisher |
MDPI AG |
series |
Journal of Clinical Medicine |
issn |
2077-0383 |
publishDate |
2020-10-01 |
description |
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. |
topic |
vascular malformations next generation sequencing tailored therapy |
url |
https://www.mdpi.com/2077-0383/9/11/3387 |
work_keys_str_mv |
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