Variable somatic TIE2 mutations in half of sporadic venous malformations

J. Soblet, N. Limaye, M. Uebelhoer, L. M. Boon, M. Vikkula

Research output: Contribution to journalArticlepeer-review

113 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)179-183
Number of pages5
JournalMolecular Syndromology
Issue number4
StatePublished - Apr 2013
Externally publishedYes


  • Hyperphosphorylation
  • Receptor tyrosine kinase
  • Somatic mutation
  • Sporadic
  • TIE2/TEK
  • Vascular malformation
  • Venous malformation

ASJC Scopus subject areas

  • Genetics(clinical)
  • Genetics


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