Molecular genetics of hemangiomas and vascular malformations

Abstract

With the recent development of next-generation sequencing technology, causative genes of relatively rare vascular anomalies have been identified. Vascular anomalies, which are classified as vascular tumors and malformations, are caused by genetic abnormalities in the RAS/MAPK or PI3K/AKT/mTOR signaling pathways and are called RASopathies and PIKopathies, respectively. Somatic activating mutations, such as GNAQ and GNA11 in congenital hemangiomas, GNA14 in tufted hemangiomas, TEK (TIE2) in venous malformations, GNAQ in capillary malformations, PIK3CA in lymphatic malformations, and MAP2K1 in arteriovenous malformations, have been reported as causative genes. We performed next-generation sequencing analysis of formalin-fixed, paraffin-embedded tissue specimens from patients with Klippel-Trenaunay syndrome. We detected PIK3CA missense mutations in 86% of the cases. The identification of common causative genes in vascular anomalies associated with cancer is expanding the application of anticancer drugs through drug repositioning.