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Nat Genet. 2014 Apr;46(4):376-379. doi: 10.1038/ng.2921. Epub 2014 Mar 16.

Recurrent PTPRB and PLCG1 mutations in angiosarcoma.

Author information

1
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK.
2
Department of Paediatrics, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK.
3
The Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, OX3 9DS, UK.
4
Human Genome Laboratory, Department of Human Genetics, VIB and KU Leuven, B-3000 Leuven, Belgium.
5
Histopathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex, HA7 4LP, UK.
6
University College London Cancer Institute, Huntley Street, London, WC1E 6BT, UK.
7
Department of Oncology, Oslo University Hospital, N-0310 Oslo, Norway.
8
The K.G. Jebsen Center for Breast Cancer Research, University of Oslo, N-0424 Oslo, Norway.
9
Institute of Structural and Molecular Biology, Division of Biosciences, University College London, London WC1E 6BT, UK.
10
Division of Molecular Structure, MRC-National Institute for Medical Research, Mill Hill, London NW7 1AA, UK.
11
Department of Pathology, John Radcliffe Hospital, Oxford, OX3 9DS, UK.
12
M. D. Anderson Cancer Center, The University of Texas, 1901 East Road, Houston, Texas 77054, USA.
13
Bone Tumour Reference Centre, Institute of Pathology, University Hospital Basel, Basel, Institute for Applied Cancer Science, Switzerland.
14
Pfizer Oncology, 10555 Science Center Dr, La Jolla, CA, 92121.
15
Department of Haematology, Addenbrooke's Hospital, Cambridge, UK.
16
Department of Haematology, University of Cambridge, Hills Road, Cambridge, CB2 2XY, UK.
#
Contributed equally

Abstract

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.Arg707Gln missense variant in 3 of 34 cases (9%). Overall, 15 of 39 tumors (38%) harbored at least one driver mutation in angiogenesis signaling genes. Our findings inform and reinforce current therapeutic efforts to target angiogenesis signaling in angiosarcoma.

PMID:
24633157
PMCID:
PMC4032873
DOI:
10.1038/ng.2921
[Indexed for MEDLINE]
Free PMC Article

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