Clonal diversification and histogenesis of malignant germ cell tumours.
Journal
Nature communications
ISSN: 2041-1723
Titre abrégé: Nat Commun
Pays: England
ID NLM: 101528555
Informations de publication
Date de publication:
11 08 2022
11 08 2022
Historique:
received:
26
01
2022
accepted:
13
06
2022
entrez:
11
8
2022
pubmed:
12
8
2022
medline:
16
8
2022
Statut:
epublish
Résumé
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.
Identifiants
pubmed: 35953478
doi: 10.1038/s41467-022-31375-4
pii: 10.1038/s41467-022-31375-4
pmc: PMC9372159
doi:
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
4272Subventions
Organisme : Cancer Research UK
ID : 27176
Pays : United Kingdom
Organisme : Department of Health
Pays : United Kingdom
Organisme : Cancer Research UK
ID : 27114
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C9685/A25117
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C9380/A25138
Pays : United Kingdom
Organisme : Wellcome Trust
Pays : United Kingdom
Organisme : Cancer Research UK
ID : C66259/A27114
Pays : United Kingdom
Informations de copyright
© 2022. Crown.
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