Journal article
Mosaic overgrowth with fibroadipose hyperplasia is caused by somatic activating mutations in PIK3CA
MJ Lindhurst, VER Parker, F Payne, JC Sapp, S Rudge, J Harris, AM Witkowski, Q Zhang, MP Groeneveld, CE Scott, A Daly, SM Huson, LL Tosi, ML Cunningham, TN Darling, J Geer, Z Gucev, VR Sutton, C Tziotzios, AK Dixon Show all
Nature Genetics | NATURE PUBLISHING GROUP | Published : 2012
DOI: 10.1038/ng.2332
Abstract
The phosphatidylinositol 3-kinase (PI3K)-AKT signaling pathway is critical for cellular growth and metabolism. Correspondingly, loss of function of PTEN, a negative regulator of PI3K, or activating mutations in AKT1, AKT2 or AKT3 have been found in distinct disorders featuring overgrowth or hypoglycemia. We performed exome sequencing of DNA from unaffected and affected cells from an individual with an unclassified syndrome of congenital progressive segmental overgrowth of fibrous and adipose tissue and bone and identified the cancer-associated mutation encoding p.His1047Leu in PIK3CA, the gene that encodes the p110Î ± catalytic subunit of PI3K, only in affected cells. Sequencing of PIK3CA in..
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Awarded by National Institute for Health Research
Funding Acknowledgements
The authors thank L. Ivey, J.J. Johnston, V. Tasic, M. Walters and E. Choolun for support and advice. The authors are especially grateful to the subjects who participated in this research study and to the Proteus Syndrome Foundations of the United States and United Kingdom, who have supported and encouraged these individuals and our research efforts. V.E.R.P., S.O., D.B.S., I.B. and R.K.S. were supported by the Wellcome Trust (grants 097721/Z/11/Z, 80952/Z/06/Z, 078986/Z/06/Z, 098051/Z/05/Z and 091551/Z/10/Z), the UK Medical Research Council Centre for Obesity and Related Disorders and the UK National Institute for Health Research (NIHR) Cambridge Biomedical Research Centre. L.G.B., M.J.L., J.C.S. and A.M.W. were supported by the Intramural Research Program of the National Human Genome Research Institute. S.R., Q.Z. and M.J.O.W. were supported by the Biotechnology and Biological Sciences Research Council (BBSRC). We are grateful for access to exome sequence data from the CoLaus cohort, which was sequenced as part of a partnership between the Wellcome Trust Sanger Institute, the CoLaus principal investigators and the Quantitative Sciences department of GlaxoSmithKline. S.M.H. is supported by the Manchester NIHR Biomedical Research Centre.