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Nat Commun. 2017 Oct 12;8(1):890. doi: 10.1038/s41467-017-01026-0.

The driver landscape of sporadic chordoma.

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, Cambridge, CB2 0QQ, UK.
3
Corpus Christi College, Cambridge, CB2 1RH, UK.
4
Los Alamos National Laboratory, Los Alamos, NM, 87545, USA.
5
UCL Great Ormond Street Institute of Child Health, London, WC1N 1EH, UK.
6
Department of Paediatric Laboratory Medicine, The Hospital for Sick Children, Toronto, ON, Canada, M5G 1X8.
7
Department of Genomic Medicine, MD Anderson Cancer Center, University of Texas, Houston, TX, 77030, USA.
8
University of British Columbia, Vancouver, BC, Canada, V6T 1Z4.
9
Bone Tumour Reference Centre, Institute of Pathology, University Hospital Basel, University of Basel, 4031, Basel, Switzerland.
10
Division of Neuropathology and Department of Neurodegenerative Disease, The National Hospital for Neurology and Neurosurgery, University College Hospital NHS Foundation Trust and UCL Institute of Neurology, London, WC1N 3BG, UK.
11
Department of Pathology and Laboratory Medicine, Mount Sinai Hospital, Toronto, ON, Canada, M5G 1X5.
12
Chordoma Foundation, PO Box 2127, Durham, NC, 27702, USA.
13
Department of Neurosurgery, University of California, San Francisco, CA, 94143, USA.
14
Department of Histopathology, Royal National Orthopaedic Hospital NHS Trust, Middlesex, Stanmore, HA7 4LP, UK.
15
University College London Cancer Institute, London, WC1E 6BT, UK.
16
Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire, CB10 1SA, UK. pc8@sanger.ac.uk.
17
Department of Haematology, University of Cambridge, Cambridge, CB2 2XY, UK. pc8@sanger.ac.uk.

Abstract

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.Chordoma is a rare often incurable malignant bone tumour. Here, the authors investigate driver mutations of sporadic chordoma in 104 cases, revealing duplications in notochordal transcription factor brachyury (T), PI3K signalling mutations, and mutations in LYST, a potential novel cancer gene in chordoma.

PMID:
29026114
PMCID:
PMC5638846
DOI:
10.1038/s41467-017-01026-0
[Indexed for MEDLINE]
Free PMC Article

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