Clonal diversification and histogenesis of malignant germ cell tumours.

Autor: Oliver TRW; Wellcome Sanger Institute, Hinxton, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Chappell L; Wellcome Sanger Institute, Hinxton, UK., Sanghvi R; Wellcome Sanger Institute, Hinxton, UK., Deighton L; Wellcome Sanger Institute, Hinxton, UK., Ansari-Pour N; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; MRC Molecular Haematology Unit, Weatherall Institute of Molecular Medicine, University of Oxford, Oxford, UK., Dentro SC; Wellcome Sanger Institute, Hinxton, UK.; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK., Young MD; Wellcome Sanger Institute, Hinxton, UK., Coorens THH; Wellcome Sanger Institute, Hinxton, UK., Jung H; Wellcome Sanger Institute, Hinxton, UK., Butler T; Wellcome Sanger Institute, Hinxton, UK., Neville MDC; Wellcome Sanger Institute, Hinxton, UK., Leongamornlert D; Wellcome Sanger Institute, Hinxton, UK., Sanders MA; Wellcome Sanger Institute, Hinxton, UK.; Department of Hematology, Erasmus University Medical Center, Rotterdam, The Netherlands., Hooks Y; Wellcome Sanger Institute, Hinxton, UK., Cagan A; Wellcome Sanger Institute, Hinxton, UK., Mitchell TJ; Wellcome Sanger Institute, Hinxton, UK.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Cortes-Ciriano I; European Molecular Biology Laboratory, European Bioinformatics Institute (EMBL-EBI), Cambridge, UK., Warren AY; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK., Wedge DC; Big Data Institute, Nuffield Department of Medicine, University of Oxford, Oxford, UK.; Manchester Cancer Research Centre, Division of Cancer Sciences, University of Manchester, Manchester, UK., Heer R; Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle upon Tyne, UK.; Newcastle Urology, Freeman Hospital, Newcastle upon Tyne Hospitals NHS Foundation Trust, Newcastle upon Tyne, UK., Coleman N; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Department of Pathology, University of Cambridge, Cambridge, UK., Murray MJ; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK.; Department of Pathology, University of Cambridge, Cambridge, UK., Campbell PJ; Wellcome Sanger Institute, Hinxton, UK., Rahbari R; Wellcome Sanger Institute, Hinxton, UK. rr11@sanger.ac.uk., Behjati S; Wellcome Sanger Institute, Hinxton, UK. sb31@sanger.ac.uk.; Cambridge University Hospitals NHS Foundation Trust, Cambridge, UK. sb31@sanger.ac.uk.; Department of Paediatrics, University of Cambridge, Cambridge, UK. sb31@sanger.ac.uk.
Jazyk: angličtina
Zdroj: Nature communications [Nat Commun] 2022 Aug 11; Vol. 13 (1), pp. 4272. Date of Electronic Publication: 2022 Aug 11.
DOI: 10.1038/s41467-022-31375-4
Abstrakt: 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.
(© 2022. Crown.)
Databáze: MEDLINE
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