Journal article
Somatic activating mutations in Pik3ca cause sporadic venous malformations in mice and humans
SD Castillo, E Tzouanacou, M Zaw-Thin, IM Berenjeno, VER Parker, I Chivite, M Milà-Guasch, W Pearce, I Solomon, A Angulo-Urarte, AM Figueiredo, RE Dewhurst, RG Knox, GR Clark, CL Scudamore, A Badar, TL Kalber, J Foster, DJ Stuckey, AL David Show all
Science Translational Medicine | AMER ASSOC ADVANCEMENT SCIENCE | Published : 2016
Abstract
Venous malformations (VMs) are painful and deforming vascular lesions composed of dilated vascular channels, which are present from birth. Mutations in the TEK gene, encoding the tyrosine kinase receptor TIE2, are found in about half of sporadic (nonfamilial) VMs, and the causes of the remaining cases are unknown. Sclerotherapy, widely accepted as first-line treatment, is not fully efficient, and targeted therapy for this disease remains underexplored. We have generated a mouse model that faithfully mirrors human VM through mosaic expression of Pik3caH1047R, a constitutively active mutant of the p110a isoform of phosphatidylinositol 3-kinase (PI3K), in the embryonic mesoderm. Endothelial exp..
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Awarded by Department of Health and Social Care
Funding Acknowledgements
Postdoctoral fellowships were from EMBO (ALTF 165-2013) to S.D.C., European Union (EU) Marie Curie (MEIF-CT-2005-010264) to E.T., and EU Marie Curie (PIIF-GA-2009-252846) to I.M.B. M.Z.-T. is supported by the Engineering and Physical Sciences Research Council (EPSRC) Early Career Fellowship of T.L.K. (EP/L006472/1). D.J.S. is a British Heart Foundation (BHF) Intermediate Basic Science Research Fellow (FS/15/33/31608). A.L.D. is supported by the UK National Institute for Health Research (NIHR) Joint UCL/University College London Hospitals Biomedical Research Centre. V.E.R.P. was supported by the Wellcome Trust (097721/Z/11/Z). R.K.S. is supported by the Wellcome Trust (WT098498), the Medical Research Council (MRC) (MRC_MC_UU_12012/5), and the NIHR Rare Diseases Translational Research Collaboration. R.G.K. is supported by the NIHR Rare Diseases Translational Research Collaboration. N.J.S. is partly supported by the NIHR GOSH BRC and GOSHCC. V.A.K. is funded by the Wellcome Trust, award number WT104076MA. V.W. was supported by the European Framework Programme VI (FPVI) Integrated Project "Eurostemcell." M.F.L. and A.B. are supported by the King's College London and UCL Comprehensive Cancer Imaging Centre Cancer Research UK and EPSRC, in association with the MRC and Department of Health (England). W.A.P. is supported by funding from the National Health and Medical Research Council (NHMRC) of Australia. Work in the laboratory of M.G. is supported by research grants SAF2013-46542-P and SAF2014-59950-P from MINECO (Spain), 2014-SGR-725 from the Catalan Government, the People Programme (Marie Curie Actions) from the EU's Seventh Framework Programme FP7/2007-2013/(REA grant agreement 317250), the Institute of Health Carlos III (ISC III), and the European Regional Development Fund (ERDF) under the integrated Project of Excellence no. PIE13/00022 (ONCOPROFILE). Work in the laboratory of B.V. is supported by Cancer Research UK (C23338/A15965) and the UK NIHR University College London Hospitals Biomedical Research Centre.