|
Congenital abnormality of vein
|
0.500 |
Biomarker
|
group |
BEFREE |
Gain-of-function mutations in the tyrosine kinase receptor TIE2 can cause VM and induce a ligand-independent hyperactivation of TIE2.
|
31451744 |
2019 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Moreover, c-ABL, common target of these inhibitors, was highly phosphorylated in HUVEC-TIE2-L914F and VM patient-derived ECs with activating TIE2 mutations.
|
30626204 |
2019 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
A Tie2 kinase mutation causing venous malformations increases phosphorylation rates and enhances cooperativity.
|
30638931 |
2019 |
|
Congenital abnormality of vein
|
0.500 |
Biomarker
|
group |
BEFREE |
Recent studies have identified genetic defects that result in the constantly active endothelial cell receptor tyrosine kinase TIE2/phosphoinositide 3-kinase PI3K signalling pathway as a frequent cause for VMs.
|
29668117 |
2018 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Activating somatic TIE2 gene mutations have been identified in up to 60% of VMs and PIK3CA mutations have been found in another 25%.
|
29786783 |
2018 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
A <i>TIE2</i> mutation causing arginine-to-tryptophan substitution at residue 849 (<i>TIE2-R849W</i>) is commonly identified in heredofamilial venous malformation.
|
29511374 |
2018 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
A role for an activating TIE2 mutation in the development of the dilated luminal vessels in VM, and its proposed involvement of embryonic stem cells (ESCs), led us to investigate the expression of ESC markers in subcutaneous VM (SCVM) and intramuscular VM (IMVM).
|
29046873 |
2017 |
|
Congenital abnormality of vein
|
0.500 |
Biomarker
|
group |
BEFREE |
Extracellularly, whereas angiopoietins (ANGs) are ligands of TIE2, the chaotic balance between ANG1 and ANG2 in VM is related to their effects on switching between the cell-cell/cell-extracellular matrix contact conditions and vascular quiescence/angiogenesis state, resulting in corrupted contacts.
|
28818232 |
2017 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
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.
|
26637981 |
2015 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Here, we report the analysis of a comprehensive collection of 22 TIE2 mutations identified in patients with VM, either as single amino acid substitutions or as double-mutations on the same allele.
|
26319232 |
2015 |
|
Congenital abnormality of vein
|
0.500 |
Biomarker
|
group |
BEFREE |
We tested both rapamycin and a TIE2 tyrosine kinase inhibitor (TIE2-TKI) for their effects on murine VM expansion and for their ability to inhibit mutant TIE2 signaling.
|
26258417 |
2015 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Mutations in TIE2/TEK genes cause inherited forms of venous malformations also with autosomal dominant inheritance.
|
24010650 |
2014 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
STAT1 activation by venous malformations mutant Tie2-R849W antagonizes VEGF-A-mediated angiogenic response partly via reduced bFGF production.
|
23086340 |
2013 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Mutations in the endothelial cell (EC) tyrosine kinase receptor TIE2 cause inherited and sporadic forms of venous malformation.
|
23633549 |
2013 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Additionally, TIE2 somatic mutations have been identified in about half of sporadic venous malformations.
|
22913934 |
2012 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Cutaneomucosal venous malformations are linked to the TIE2 mutation in a large Chinese family.
|
22621187 |
2012 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Recently, somatic mutations in exon 17 of the endothelial cell tyrosine kinase receptor Tie-2 (encoded by TEK) were identified in 49.1% of patients with common sporadic venous malformation, a subtype of vascular anomalies.
|
21962923 |
2011 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Hereditary cutaneomucosal venous malformations are caused by TIE2 mutations with widely variable hyper-phosphorylating effects.
|
19888299 |
2010 |
|
Congenital abnormality of vein
|
0.500 |
Biomarker
|
group |
BEFREE |
These data show that a sporadic disease may be explained by somatic changes in a gene causing rare, inherited forms and pinpoint TIE2 pathways as potential therapeutic targets for venous malformations.
|
19079259 |
2009 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Tie2-R849W mutant in venous malformations chronically activates a functional STAT1 to modulate gene expression.
|
18401423 |
2008 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
We did not detect any mutations in the two loci of the TIE2 gene that have been reported in familial venous malformations.
|
15672715 |
2004 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Homozygosity mapping excluded the following loci and/or genes: multiple cutaneous venous malformation (VMCM1; gene, TIE2) on chromosome 9p21; venous malformation with glomus cells (VMGLOM) on chromosome 1p22-p21; hereditary hemorrhagic telangiectasia type 1 (HHT1; gene, endoglin) and type 2 (HHT2; gene, activin) on chromosomes 9q34.1 and 12q11-q14, respectively; and cerebral cavernous malformation type 1 (CCM1; gene, KRIT1), type 2 (CCM2), and type 3 (CCM3) on chromosomes 7q11.2-q21, 7p15-p13, and 3q35.2-q27, respectively.
|
11932989 |
2002 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
Using linkage analysis, we have established in earlier reports that some families with inherited VMs show linkage to chromosome 9p21; the mutation causes ligand-independent activation of an endothelial cell-specific receptor tyrosine kinase, TIE-2.
|
10364524 |
1999 |
|
Congenital abnormality of vein
|
0.500 |
GeneticVariation
|
group |
BEFREE |
We conclude that an activating mutation in TIE2 causes inherited VMs in the two families and that the TIE2 signaling pathway is critical for endothelial cell-smooth muscle cell communication in venous morphogenesis.
|
8980225 |
1996 |
|
Congenital abnormality of vein
|
0.500 |
Biomarker
|
group |
HPO |
|
|
|