dc.contributor.author | Studd, JB | |
dc.contributor.author | Cornish, AJ | |
dc.contributor.author | Hoang, PH | |
dc.contributor.author | Law, P | |
dc.contributor.author | Kinnersley, B | |
dc.contributor.author | Houlston, R | |
dc.date.accessioned | 2022-02-01T16:14:17Z | |
dc.date.available | 2022-02-01T16:14:17Z | |
dc.date.issued | 2021-11-09 | |
dc.identifier.citation | Blood cancer journal, 2021, 11 (11), pp. 177 - ? | |
dc.identifier.issn | 2044-5385 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4990 | |
dc.identifier.eissn | 2044-5385 | |
dc.identifier.eissn | 2044-5385 | |
dc.identifier.doi | 10.1038/s41408-021-00570-9 | |
dc.identifier.doi | 10.1038/s41408-021-00570-9 | |
dc.description.abstract | To obtain a comprehensive picture of composite genetic driver events and clonal dynamics in subtypes of paediatric acute lymphoblastic leukaemia (ALL) we analysed tumour-normal whole genome sequencing and expression data from 361 newly diagnosed patients. We report the identification of both structural drivers, as well as recurrent non-coding variation in promoters. Additionally we found the transcriptional profile of histone gene cluster 1 and CTCF altered tumours shared hallmarks of hyperdiploid ALL suggesting a 'hyperdiploid like' subtype. ALL subtypes are driven by distinct mutational processes with AID mutagenesis being confined to ETV6-RUNX1 tumours. Subclonality is a ubiquitous feature of ALL, consistent with Darwinian evolution driving selection and expansion of tumours. Driver mutations in B-cell developmental genes (IKZF1, PAX5, ZEB2) tend to be clonal and RAS/RTK mutations subclonal. In addition to identifying new avenues for therapeutic exploitation, this analysis highlights that targeted therapies should take into account composite mutational profile and clonality. | |
dc.format | Electronic | |
dc.format.extent | 177 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | SPRINGERNATURE | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.title | Cancer drivers and clonal dynamics in acute lymphoblastic leukaemia subtypes. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-10-27 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41408-021-00570-9 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-11-09 | |
dc.relation.isPartOf | Blood cancer journal | |
pubs.issue | 11 | |
pubs.notes | Not known | |
pubs.organisational-group | /ICR | |
pubs.organisational-group | /ICR/Primary Group | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Genetics and Epidemiology/Cancer Genomics | |
pubs.publication-status | Published | |
pubs.volume | 11 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Cancer Genomics | |
dc.contributor.icrauthor | Studd, James | |
dc.contributor.icrauthor | Cornish, Alexander | |
dc.contributor.icrauthor | Law, Philip | |
dc.contributor.icrauthor | Kinnersley, Benjamin | |
dc.contributor.icrauthor | Houlston, Richard | |