Somatic Activating Mutations Cause Venous Malformation

Somatic mutations in TEK, the gene encoding endothelial cell tyrosine kinase receptor TIE2, cause more than half of sporadically occurring unifocal venous malformations (VMs). Here, we report that somatic mutations in PIK3CA, the gene encoding the catalytic p110α subunit of PI3K, cause 54% (27 out of 50) of VMs with no detected TEK mutation. The hotspot mutations c.1624G>A, c.1633G>A, and c.3140A>G (p.Glu542Lys, p.Glu545Lys, and p.His1047Arg), frequent in PIK3CA-associated cancers, overgrowth syndromes, and lymphatic malformation (LM), account for >92% of individuals who carry mutations.

Source: The American Journal of Human Genetics - December 3, 2015 Category: Genetics & Stem Cells Authors: Nisha Limaye, Jaakko Kangas, Antonella Mendola, Catherine Godfraind, Matthieu J. Schlögel, Raphael Helaers, Lauri Eklund, Laurence M. Boon, Miikka Vikkula Tags: Report Source Type: research