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Clonal diversification and histogenesis of malignant germ cell tumours

Author

Listed:
  • Thomas R. W. Oliver

    (Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust)

  • Lia Chappell

    (Wellcome Sanger Institute)

  • Rashesh Sanghvi

    (Wellcome Sanger Institute)

  • Lauren Deighton

    (Wellcome Sanger Institute)

  • Naser Ansari-Pour

    (University of Oxford
    University of Oxford)

  • Stefan C. Dentro

    (Wellcome Sanger Institute
    European Bioinformatics Institute (EMBL-EBI))

  • Matthew D. Young

    (Wellcome Sanger Institute)

  • Tim H. H. Coorens

    (Wellcome Sanger Institute)

  • Hyunchul Jung

    (Wellcome Sanger Institute)

  • Tim Butler

    (Wellcome Sanger Institute)

  • Matthew D. C. Neville

    (Wellcome Sanger Institute)

  • Daniel Leongamornlert

    (Wellcome Sanger Institute)

  • Mathijs A. Sanders

    (Wellcome Sanger Institute
    Erasmus University Medical Center)

  • Yvette Hooks

    (Wellcome Sanger Institute)

  • Alex Cagan

    (Wellcome Sanger Institute)

  • Thomas J. Mitchell

    (Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust)

  • Isidro Cortes-Ciriano

    (European Bioinformatics Institute (EMBL-EBI))

  • Anne Y. Warren

    (Cambridge University Hospitals NHS Foundation Trust)

  • David C. Wedge

    (University of Oxford
    University of Manchester)

  • Rakesh Heer

    (Newcastle University
    Newcastle upon Tyne Hospitals NHS Foundation Trust)

  • Nicholas Coleman

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Matthew J. Murray

    (Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

  • Peter J. Campbell

    (Wellcome Sanger Institute)

  • Raheleh Rahbari

    (Wellcome Sanger Institute)

  • Sam Behjati

    (Wellcome Sanger Institute
    Cambridge University Hospitals NHS Foundation Trust
    University of Cambridge)

Abstract

Germ cell tumours (GCTs) are a collection of benign and malignant neoplasms derived from primordial germ cells. They are uniquely able to recapitulate embryonic and extraembryonic tissues, which carries prognostic and therapeutic significance. The developmental pathways underpinning GCT initiation and histogenesis are incompletely understood. Here, we study the relationship of histogenesis and clonal diversification in GCTs by analysing the genomes and transcriptomes of 547 microdissected histological units. We find no correlation between genomic and histological heterogeneity. However, we identify unifying features including the retention of fetal developmental transcripts across tissues, expression changes on chromosome 12p, and a conserved somatic evolutionary sequence of whole genome duplication followed by clonal diversification. While this pattern is preserved across all GCTs, the developmental timing of the duplication varies between prepubertal and postpubertal cases. In addition, tumours of younger children exhibit distinct substitution signatures which may lend themselves as potential biomarkers for risk stratification. Our findings portray the extensive diversification of GCT tissues and genetic subclones as randomly distributed, while identifying overarching transcriptional and genomic features.

Suggested Citation

  • Thomas R. W. Oliver & Lia Chappell & Rashesh Sanghvi & Lauren Deighton & Naser Ansari-Pour & Stefan C. Dentro & Matthew D. Young & Tim H. H. Coorens & Hyunchul Jung & Tim Butler & Matthew D. C. Nevill, 2022. "Clonal diversification and histogenesis of malignant germ cell tumours," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
  • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-31375-4
    DOI: 10.1038/s41467-022-31375-4
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