Molecular and genetic aspects of hemangiomas and vascular malformations

Abstract

Vascular anomalies are localized developmental defects of the vasculature. They include vascular tumors, primarily infantile hemangioma, and vascular malformations, which are categorized by the compartment they affect into capillary, lymphatic, venous, arterial, and combined malformations. While typically isolated and sporadic, hemangiomas and vascular malformations can occur as inherited traits or as part of certain syndromes. The identification of the genetic changes that cause disease holds out the promise of accurate (molecular) diagnosis, as well as insights into disease mechanisms and novel targets for improved therapy. The advances initially made were largely confined to rare, familial forms, with much less known about the bases of the common sporadic versions of vascular malformations. The shift toward the analysis of affected tissues in addition to blood samples has now proven to be key in improving our understanding, as it is becoming increasingly evident that somatic changes play an important role in these developmental disorders. In addition, rapidly evolving next-generation sequencing techniques allow for unprecedented throughput and depth of coverage, greatly increasing the ability to detect mosaic changes anywhere in the exome or genome. Expression profiling and functional studies, in vitro and in animal models, have in parallel begun to uncover how the aberrant genes affect the different cellular and molecular components of the vasculature.