Variable Somatic TIE2 Mutations in Half of Sporadic Venous Malformations

Molecular Syndromology

M. Vikkula¹  J. Soblet¹  M. Uebelhoer¹  N. Limaye¹  L.M. Boon¹ 

[1] aLaboratory of Human Molecular Genetics, de Duve Institute, Université catholique de Louvain, Brussels, Belgium

关键词: Hyperphosphorylation;    Receptor tyrosine kinase;    Somatic mutation;    Sporadic;    TIE2/TEK;    Vascular malformation;    Venous malformation
;   

DOI  :  10.1159/000348327

学科分类：基础医学

来源: S Karger AG

【 摘 要 】

Venous malformations (VMs) are the most frequent vascular malformations referred to specialized vascular anomaly centers. A rare (1-2%) familial form, termed cutaneomucosal venous malformation (VMCM), is caused by gain-of-function mutations in TIE2. More recently, sporadic VMs, characterized by the presence of large unifocal lesions, were shown to be caused by somatic mutations in TIE2. These include a frequent L914F change, and a series of double mutations in cis. All of which cause ligand-independent receptor hyperphosphorylation in vitro. Here, we expanded our study to assess the range of mutations that cause sporadic VM. To test for somatic changes, we screened the entire coding region of TIE2 in cDNA from resected VMs by direct sequencing. We detected TIE2 mutations in 17/30 (56.7%) of the samples. In addition to previously detected mutations, we identified 7 novel somatic intracellular TIE2 mutations in sporadic VMs, including 3 that cause premature protein truncation.

【 授权许可】

Unknown