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dc.contributor.authorOliver, Thomas RW
dc.contributor.authorChappell, Lia
dc.contributor.authorSanghvi, Rashesh
dc.contributor.authorDeighton, Lauren
dc.contributor.authorAnsari-Pour, Naser
dc.contributor.authorDentro, Stefan C
dc.contributor.authorYoung, Matthew D
dc.contributor.authorCoorens, Tim HH
dc.contributor.authorJung, Hyunchul
dc.contributor.authorButler, Tim
dc.contributor.authorNeville, Matthew DC
dc.contributor.authorLeongamornlert, Daniel
dc.contributor.authorSanders, Mathijs A
dc.contributor.authorHooks, Yvette
dc.contributor.authorCagan, Alex
dc.contributor.authorMitchell, Thomas J
dc.contributor.authorCortes-Ciriano, Isidro
dc.contributor.authorWarren, Anne Y
dc.contributor.authorWedge, David C
dc.contributor.authorHeer, Rakesh
dc.contributor.authorColeman, Nicholas
dc.contributor.authorMurray, Matthew J
dc.contributor.authorCampbell, Peter J
dc.contributor.authorRahbari, Raheleh
dc.contributor.authorBehjati, Sam
dc.date.accessioned2022-03-09T00:31:01Z
dc.date.available2022-03-09T00:31:01Z
dc.date.issued2022-08-11
dc.identifier.issn2041-1723
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/334797
dc.description.abstractGerm 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.
dc.publisherSpringer Science and Business Media LLC
dc.rightsCreative Commons Attribution 4.0 International License
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/
dc.titleClonal diversification and histogenesis of malignant germ cell tumours.
dc.typeArticle
dc.publisher.departmentDepartment of Pathology
dc.date.updated2022-03-08T12:00:26Z
prism.publicationNameNat Commun
dc.identifier.doi10.17863/CAM.82227
dcterms.dateAccepted2022-06-13
rioxxterms.versionofrecord10.1038/s41467-022-31375-4
rioxxterms.versionVoR
dc.contributor.orcidOliver, Thomas RW [0000-0003-4306-0102]
dc.contributor.orcidChappell, Lia [0000-0002-2317-3524]
dc.contributor.orcidSanghvi, Rashesh [0000-0002-7703-9216]
dc.contributor.orcidAnsari-Pour, Naser [0000-0003-0908-0484]
dc.contributor.orcidYoung, Matthew D [0000-0003-0937-5290]
dc.contributor.orcidCoorens, Tim HH [0000-0002-5826-3554]
dc.contributor.orcidButler, Tim [0000-0001-5803-1035]
dc.contributor.orcidNeville, Matthew DC [0000-0001-5816-7936]
dc.contributor.orcidLeongamornlert, Daniel [0000-0002-3486-3168]
dc.contributor.orcidCagan, Alex [0000-0002-7857-4771]
dc.contributor.orcidMitchell, Thomas J [0000-0003-0761-9503]
dc.contributor.orcidCortes-Ciriano, Isidro [0000-0002-2036-494X]
dc.contributor.orcidWedge, David C [0000-0002-7572-3196]
dc.contributor.orcidMurray, Matthew J [0000-0002-4480-1147]
dc.contributor.orcidCampbell, Peter J [0000-0002-3921-0510]
dc.contributor.orcidRahbari, Raheleh [0000-0002-1839-7785]
dc.contributor.orcidBehjati, Sam [0000-0002-6600-7665]
dc.identifier.eissn2041-1723
rioxxterms.typeJournal Article/Review
pubs.funder-project-idCancer Research UK (A25117)
cam.issuedOnline2022-08-11
cam.orpheus.success2022/08/22
cam.orpheus.counter13
cam.depositDate2022-03-08
pubs.licence-identifierapollo-deposit-licence-2-1
pubs.licence-display-nameApollo Repository Deposit Licence Agreement


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Creative Commons Attribution 4.0 International License
Except where otherwise noted, this item's licence is described as Creative Commons Attribution 4.0 International License