Somatic mutations in exon 17 of the TEK gene in vascular tumors and vascular malformations

Ye, Caisheng; Pan, Langxing; Huang, Yongbo; Ye, Runyi; Han, Anqin; Li, Songqi; Li, Xiaoxi; Wang, Shenming

doi:10.1016/j.jvs.2011.06.098

Cited by 38 publications

(24 citation statements)

References 29 publications

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“…These mutations were confirmed via Sanger sequencing ( Supplementary Figure S2 online ). Neither dataset had mutations in genes previously identified in vascular tumors or malformations, including TEK, RASA1, CCM1/2/3, GLMN, VEGRF3, FOXC2, SOX18, ACVRLK1, MADH4, and ENG ( Ye et al , 2011 ). No evidence of secondary somatic variants or regions of loss of heterozygosity (LOH) was found, suggesting both cases are true somatic RASopathies ( Supplementary Figure S3 online ).…”

Section: To the Editormentioning

confidence: 99%

“…Previously identified somatic mutations in vascular tumors or malformations have involved key angiogenic players such as TEK , a tyrosine kinase involved in vascular remodeling, and the VEGFR receptor ( Ye et al , 2011 ). While somatic mutation in RAS has not been reported in human PG or vascular tumors, RAS signaling is associated with angiogenesis and vascular proliferation ( Kranenburg et al , 2004 ).…”

Section: To the Editormentioning

confidence: 99%

See 1 more Smart Citation

Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma

Lim

Douglas

et al. 2015

Journal of Investigative Dermatology

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Section: To the Editormentioning

confidence: 99%

Section: To the Editormentioning

confidence: 99%

Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma

Lim

Douglas

et al. 2015

Journal of Investigative Dermatology

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“…[ 11 ] Ye et al . [ 17 ] have proposed the pathogenetic relevance of the occasional detection of mutation in the endothelial cell tyrosine kinase receptor Tie-2. Instead, Kempf et al .…”

Section: Discussionmentioning

confidence: 99%

Angiolymphoid hyperplasia with eosinophilia and entrapment of the ulnar nerve

H¹,

D²,

Ricci³

et al. 2016

Surg Neurol Int

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Background:The angiolymphoid hyperplasia with eosinophilia (ALHE) is a sporadic vasoproliferative lesion of uncertain etiology involving the skin and the subcutaneous tissue. Occasionally, it involves also the large arteries compressing the near nerves. ALHE is commonly confused with Kimura's disease because of their clinical and histological similarities.Case Description:We report a case of a 52-year-old female suffering from a 6-month pain and paresthesias in the fourth and fifth finger of the right hand. The angiography showed a pseudoaneurysm in the proximal third of the right ulnar artery. A complete surgical excision of the vascular lesion was undertaken. The lesion forced the right ulnar nerve. The histopathological diagnosis deposed for ALHE.Conclusion:Up to now, literature has described 8 cases of ALHE involving the arteries, and only one case originating from the ulnar nerve. The authors report a case of a female with ALHE involving the ulnar artery that compressed the ulnar nerve. Clinical aspects, radiological features, surgical treatment, and operative findings are discussed reviewing the pertinent literature.

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“…Somatic L914F (2740 C T) as the most frequent change has been con rmed in a large proportion of sporadic VMs [14]. Remarkably, TIE2 autophosphorylation increase in all identi ed TIE2 mutant ECs [15][16][17]. In addition, human umbilical vein endothelial cells (HUVECs) engineered to express TIE2-L914F recapitulate VMs when injected in immunode cient mice [18].…”

Section: Introductionmentioning

confidence: 99%

AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

Jiang

Si²,

Huang

et al. 2020

Preprint

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Background: Venous malformations (VMs), most of which associated with activating mutations in the endothelial cells (ECs) tyrosine kinase receptor TIE2, are characterized by dilated and immature veins with scarce smooth muscle cells (SMCs) coverage. However, the underlying mechanism of interaction between ECs and SMCs responsible for VMs has not been fully understood.Methods: Here, we screened 5 patients with TIE2-L914F mutation who were diagnosed with VMs by SNP sequencing, and we compared the expression of platelet-derived growth factor beta (PDGFB) and α-SMA in TIE2 mutant veins and normal veins by immunohistochemistry. In vitro, we generated TIE2-L914F-expressing human umbilical vein endothelial cells (HUVECs) and performed BrdU, CCK-8, transwell and tube formation experiments on none-transfected and transfected ECs. Then we investigated the effects of rapamycin (RAPA) on cellular characteristics. Next we established a co-culture system and investigated the role of AKT/FOXO1/PDGFB in regulating cross-talking of mutant ECs and SMCs.Results: VMs with TIE2-L914F mutation showed lower expression of PDGFB and α-SMA than normal veins. TIE2 mutant ECs revealed enhanced cell viability and motility, and decreased tube formation, whereas these phenotypes could be reversed by rapamycin. Mechanically, RAPA ameliorated the physiological function of mutant ECs by inhibiting AKT-mTOR pathway, but also facilitated the nuclear location of FOXO1 and the expression of PDGFB in mutant ECs, and then improved paracrine interactions between ECs and SMCs. Moreover, TIE2 mutant ECs strongly accelerated the transition of SMCs from contractile phenotype to synthetic phenotype, whereas RAPA could prevent the phenotype transition of SMCs.Conclusions: Our data demonstrate a previously unknown mechanistic linkage of AKT-mTOR/FOXO1 pathway between mutant ECs and SMCs in modulating venous dysmorphogenesis, and AKT/FOXO1 axis might be a potential therapeutic target for the recovery of TIE2-mutation causing VMs.

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Somatic mutations in exon 17 of the TEK gene in vascular tumors and vascular malformations

Cited by 38 publications

References 29 publications

Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma

Somatic Activating RAS Mutations Cause Vascular Tumors Including Pyogenic Granuloma

Angiolymphoid hyperplasia with eosinophilia and entrapment of the ulnar nerve

AKT/FOXO1 axis links cross-talking of endothelial cell and pericyte in TIE2-mutated venous malformations

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