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- Title
Clonal diversification and histogenesis of malignant germ cell tumours.
- Authors
Oliver, Thomas R. W.; Chappell, Lia; Sanghvi, Rashesh; Deighton, Lauren; Ansari-Pour, Naser; Dentro, Stefan C.; Young, Matthew D.; Coorens, Tim H. H.; Jung, Hyunchul; Butler, Tim; Neville, Matthew D. C.; Leongamornlert, Daniel; Sanders, Mathijs A.; Hooks, Yvette; Cagan, Alex; Mitchell, Thomas J.; Cortes-Ciriano, Isidro; Warren, Anne Y.; Wedge, David C.; Heer, Rakesh
- 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. The molecular characterisation of germ cell tumours (GCT) is necessary to understand their development and histological diversification. Here, the authors use whole-genome and transcriptome sequencing of GCTs across distinct histologies to reveal their somatic evolution and clonal diversification, as well as identify several putative biomarkers for treatment stratification.
- Subjects
HISTOGENESIS; GERM cells; CANCER cells; WHOLE genome sequencing; BENIGN tumors; FETAL tissues; PUBERTY
- Publication
Nature Communications, 2022, Vol 13, Issue 1, p1
- ISSN
2041-1723
- Publication type
Article
- DOI
10.1038/s41467-022-31375-4