Clonality and evolutionary history of rhabdomyosarcoma.

Chen, L; Shern, JF; Wei, JS; Yohe, ME; Song, YK; Hurd, L; Liao, H; Catchpoole, D; Skapek, SX; Barr, FG; Hawkins, DS; Khan, J

Clonality and evolutionary history of rhabdomyosarcoma.

Chen, L Shern, JF Wei, JS Yohe, ME Song, YK Hurd, L Liao, H Catchpoole, D Skapek, SX Barr, FG Hawkins, DS Khan, J

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Publisher:: Public Library of Science (PLoS)
Publication Type:: Journal Article
Citation:: PLoS Genet, 2015, 11, (3), pp. e1005075
Issue Date:: 2015-03

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Field	Value	Language
dc.contributor.author	Chen, L
dc.contributor.author	Shern, JF
dc.contributor.author	Wei, JS
dc.contributor.author	Yohe, ME
dc.contributor.author	Song, YK
dc.contributor.author	Hurd, L
dc.contributor.author	Liao, H
dc.contributor.author	Catchpoole, D
dc.contributor.author	Skapek, SX
dc.contributor.author	Barr, FG
dc.contributor.author	Hawkins, DS
dc.contributor.author	Khan, J
dc.date.accessioned	2022-04-11T04:37:16Z
dc.date.available	2015-02-16
dc.date.available	2022-04-11T04:37:16Z
dc.date.issued	2015-03
dc.identifier.citation	PLoS Genet, 2015, 11, (3), pp. e1005075
dc.identifier.issn	1553-7390
dc.identifier.issn	1553-7404
dc.identifier.uri	http://hdl.handle.net/10453/156058
dc.description.abstract	To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and mutations in RAS pathway genes occur early in the evolutionary history of the PAX-fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non-RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than PFN-RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the whole genome duplication. Our findings provide information critical to the understanding of tumorigenesis of RMS.
dc.format	Electronic-eCollection
dc.language	eng
dc.publisher	Public Library of Science (PLoS)
dc.relation.ispartof	PLoS Genet
dc.relation.isbasedon	10.1371/journal.pgen.1005075
dc.rights	info:eu-repo/semantics/openAccess
dc.subject	0604 Genetics
dc.subject.classification	Developmental Biology
dc.subject.mesh	Adolescent
dc.subject.mesh	Child
dc.subject.mesh	Child, Preschool
dc.subject.mesh	Chromosomes, Human, Pair 11
dc.subject.mesh	Genome, Human
dc.subject.mesh	Genome-Wide Association Study
dc.subject.mesh	Humans
dc.subject.mesh	Infant
dc.subject.mesh	Loss of Heterozygosity
dc.subject.mesh	Oncogene Proteins, Fusion
dc.subject.mesh	Paired Box Transcription Factors
dc.subject.mesh	Rhabdomyosarcoma
dc.subject.mesh	Sequence Analysis, DNA
dc.subject.mesh	Chromosomes, Human, Pair 11
dc.subject.mesh	Humans
dc.subject.mesh	Rhabdomyosarcoma
dc.subject.mesh	Oncogene Proteins, Fusion
dc.subject.mesh	Sequence Analysis, DNA
dc.subject.mesh	Loss of Heterozygosity
dc.subject.mesh	Genome, Human
dc.subject.mesh	Adolescent
dc.subject.mesh	Child
dc.subject.mesh	Child, Preschool
dc.subject.mesh	Infant
dc.subject.mesh	Paired Box Transcription Factors
dc.subject.mesh	Genome-Wide Association Study
dc.title	Clonality and evolutionary history of rhabdomyosarcoma.
dc.type	Journal Article
utslib.citation.volume	11
utslib.location.activity	United States
utslib.for	0604 Genetics
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Engineering and Information Technology
utslib.copyright.status	open_access	*
dc.date.updated	2022-04-11T04:37:09Z
pubs.issue	3
pubs.publication-status	Published online
pubs.volume	11
utslib.citation.issue	3

Abstract:

To infer the subclonality of rhabdomyosarcoma (RMS) and predict the temporal order of genetic events for the tumorigenic process, and to identify novel drivers, we applied a systematic method that takes into account germline and somatic alterations in 44 tumor-normal RMS pairs using deep whole-genome sequencing. Intriguingly, we find that loss of heterozygosity of 11p15.5 and mutations in RAS pathway genes occur early in the evolutionary history of the PAX-fusion-negative-RMS (PFN-RMS) subtype. We discover several early mutations in non-RAS mutated samples and predict them to be drivers in PFN-RMS including recurrent mutation of PKN1. In contrast, we find that PAX-fusion-positive (PFP) subtype tumors have undergone whole-genome duplication in the late stage of cancer evolutionary history and have acquired fewer mutations and subclones than PFN-RMS. Moreover we predict that the PAX3-FOXO1 fusion event occurs earlier than the whole genome duplication. Our findings provide information critical to the understanding of tumorigenesis of RMS.

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http://hdl.handle.net/10453/156058