biostudies-literatureBehjati SCancer Research UKNational Institute for Health Research (NIHR)NCI NIH HHSWellcome Trust376-379https://www.ebi.ac.uk/biostudies/studies/S-EPMC4032873biostudies-literatureUnknown46(4)Angiosarcoma is an aggressive malignancy that arises spontaneously or secondarily to ionizing radiation or chronic lymphoedema. Previous work has identified aberrant angiogenesis, including occasional somatic mutations in angiogenesis signaling genes, as a key driver of angiosarcoma. Here we employed whole-genome, whole-exome and targeted sequencing to study the somatic changes underpinning primary and secondary angiosarcoma. We identified recurrent mutations in two genes, PTPRB and PLCG1, which are intimately linked to angiogenesis. The endothelial phosphatase PTPRB, a negative regulator of vascular growth factor tyrosine kinases, harbored predominantly truncating mutations in 10 of 39 tumors (26%). PLCG1, a signal transducer of tyrosine kinases, encoded a recurrent, likely activating p.ANature geneticsRecurrent PTPRB and PLCG1 mutations in angiosarcoma.PMC4032873P30 CA016672WT088340MA08834016567098051NF-SI-0611-1016309386711359077012/Z/05/ZK08 CA160443Gundem GRavi VCampbell PJMartincorena IZhang JPillay NVollan HKMMahadeshwar HProtopopov ALittle LKhatri BIngram DFlanagan AMMartin SBaumhoer DPatil MMcDermott UPapaemmanuil EAmary MFTeague JWBehjati STorres KEAl Sannaa GABunney TDKoss HLazar AJRoxanis IVan Loo PHardy CSheldon HWedge DCTang JKatan MHalai DStratton MRSong XRamakrishna MCooke SLFutreal PAButler ATirabosco RBoshoff CHarris ATarpey PSCao YSteers GGumbs CMudie LJoseph ORSeth SfalseRecurrent PTPRB and PLCG1 mutations in angiosarcoma.Angiosarcoma is an aggressive malignancy that arises spontaneously or secondarily to ionizing radiation or chronic lymphoedema. Previous work has identified aberrant angiogenesis, including occasional somatic mutations in angiogenesis signaling genes, as a key driver of angiosarcoma. Here we employed whole-genome, whole-exome and targeted sequencing to study the somatic changes underpinning primary and secondary angiosarcoma. We identified recurrent mutations in two genes, PTPRB and PLCG1, which are intimately linked to angiogenesis. The endothelial phosphatase PTPRB, a negative regulator of vascular growth factor tyrosine kinases, harbored predominantly truncating mutations in 10 of 39 tumors (26%). PLCG1, a signal transducer of tyrosine kinases, encoded a recurrent, likely activating p.A2014-01-01T00:00:00Z2014 Apr2026-04-17T15:27:23.019Z2019-03-27T01:28:49ZS-EPMC40328732463315710.1038/ng.2921