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Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways.
Steele, Christopher D; Tarabichi, Maxime; Oukrif, Dahmane; Webster, Amy P; Ye, Hongtao; Fittall, Matthew; Lombard, Patrick; Martincorena, Iñigo; Tarpey, Patrick S; Collord, Grace; Haase, Kerstin; Strauss, Sandra J; Berisha, Fitim; Vaikkinen, Heli; Dhami, Pawan; Jansen, Marnix; Behjati, Sam; Amary, M Fernanda; Tirabosco, Roberto; Feber, Andrew; Campbell, Peter J; Alexandrov, Ludmil B; Van Loo, Peter; Flanagan, Adrienne M; Pillay, Nischalan.
Affiliation
  • Steele CD; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK.
  • Tarabichi M; Cancer Genomics Laboratory, The Francis Crick Institute, London NW1 1BF, UK.
  • Oukrif D; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK.
  • Webster AP; Department of Cancer Biology, UCL Cancer Institute, University College London, London, UK.
  • Ye H; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Fittall M; Cancer Genomics Laboratory, The Francis Crick Institute, London NW1 1BF, UK.
  • Lombard P; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK.
  • Martincorena I; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Tarpey PS; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Collord G; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK.
  • Haase K; Cancer Genomics Laboratory, The Francis Crick Institute, London NW1 1BF, UK.
  • Strauss SJ; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK; Department of Oncology, University College London Hospital NHS Foundation Trust, London, NW1 2PG, UK.
  • Berisha F; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Vaikkinen H; Genomics and Genome Engineering Core Facility, CRUK-UCL Centre, Cancer Institute, University College London, London WC1E 6BT, UK; Research Department of Oncology, Cancer Institute, University College London, London WC1E 6BT, UK.
  • Dhami P; Genomics and Genome Engineering Core Facility, CRUK-UCL Centre, Cancer Institute, University College London, London WC1E 6BT, UK.
  • Jansen M; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK; Department of Cellular Pathology, University College London Hospital NHS Foundation Trust, London NW1 2BU, UK.
  • Behjati S; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK; Department of Paediatrics, University of Cambridge, Cambridge CB2 0QQ, UK.
  • Amary MF; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Tirabosco R; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Feber A; Department of Targeted Intervention, Division of Surgery and Interventional Science, University College London, London WC1E 6BT, UK.
  • Campbell PJ; Cancer Genome Project, Wellcome Trust Sanger Institute, Wellcome Trust Genome Campus, Hinxton, Cambridgeshire CB10 1SA, UK; Department of Haematology, University of Cambridge, Hills Road, Cambridge CB2 2XY, UK.
  • Alexandrov LB; Department of Cellular and Molecular Medicine, University of California, San Diego 92093, USA.
  • Van Loo P; Cancer Genomics Laboratory, The Francis Crick Institute, London NW1 1BF, UK; Department of Human Genetics, University of Leuven, 3000 Leuven, Belgium.
  • Flanagan AM; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK.
  • Pillay N; Research Department of Pathology, Cancer Institute, University College London, London WC1E 6BT, UK; Department of Cellular and Molecular Pathology, Royal National Orthopaedic Hospital NHS Trust, Stanmore, Middlesex HA7 4LP, UK. Electronic address: n.pillay@ucl.ac.uk.
Cancer Cell ; 35(3): 441-456.e8, 2019 03 18.
Article in En | MEDLINE | ID: mdl-30889380
ABSTRACT
Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling. We identified whole genome duplication as a prevalent and pernicious force in USARC tumorigenesis. Using mathematical deconvolution strategies to unravel the complex copy-number profiles and mutational timing models we infer distinct evolutionary pathways of these rare cancers. In addition, 15% of tumors exhibited raised mutational burdens that correlated with gene expression signatures of immune infiltration, and good prognosis.
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma / Sequence Analysis, DNA / DNA Methylation / Gene Expression Profiling Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2019 Document type: Article Affiliation country:
Fulltext
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Full text: 1 Collection: 01-internacional Database: MEDLINE Main subject: Sarcoma / Sequence Analysis, DNA / DNA Methylation / Gene Expression Profiling Type of study: Prognostic_studies Limits: Humans Language: En Journal: Cancer Cell Journal subject: NEOPLASIAS Year: 2019 Document type: Article Affiliation country: