dc.contributor.author | von Loga, K | |
dc.contributor.author | Woolston, A | |
dc.contributor.author | Punta, M | |
dc.contributor.author | Barber, LJ | |
dc.contributor.author | Griffiths, B | |
dc.contributor.author | Semiannikova, M | |
dc.contributor.author | Spain, G | |
dc.contributor.author | Challoner, B | |
dc.contributor.author | Fenwick, K | |
dc.contributor.author | Simon, R | |
dc.contributor.author | Marx, A | |
dc.contributor.author | Sauter, G | |
dc.contributor.author | Lise, S | |
dc.contributor.author | Matthews, N | |
dc.contributor.author | Gerlinger, M | |
dc.date.accessioned | 2019-12-06T15:10:07Z | |
dc.date.issued | 2020-01-16 | |
dc.identifier.citation | Nature communications, 2020, 11 (1), pp. 139 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/3447 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-019-13915-7 | |
dc.description.abstract | Mismatch repair deficient (dMMR) gastro-oesophageal adenocarcinomas (GOAs) show better outcomes than their MMR-proficient counterparts and high immunotherapy sensitivity. The hypermutator-phenotype of dMMR tumours theoretically enables high evolvability but their evolution has not been investigated. Here we apply multi-region exome sequencing (MSeq) to four treatment-naive dMMR GOAs. This reveals extreme intratumour heterogeneity (ITH), exceeding ITH in other cancer types >20-fold, but also long phylogenetic trunks which may explain the exquisite immunotherapy sensitivity of dMMR tumours. Subclonal driver mutations are common and parallel evolution occurs in RAS, PIK3CA, SWI/SNF-complex genes and in immune evasion regulators. MSeq data and evolution analysis of single region-data from 64 MSI GOAs show that chromosome 8 gains are early genetic events and that the hypermutator-phenotype remains active during progression. MSeq may be necessary for biomarker development in these heterogeneous cancers. Comparison with other MSeq-analysed tumour types reveals mutation rates and their timing to determine phylogenetic tree morphologies. | |
dc.format | Electronic | |
dc.format.extent | 139 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PUBLISHING GROUP | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.title | Extreme intratumour heterogeneity and driver evolution in mismatch repair deficient gastro-oesophageal cancer. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2019-12-05 | |
rioxxterms.versionofrecord | 10.1038/s41467-019-13915-7 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2020-01-16 | |
rioxxterms.type | Journal Article/Review | |
dc.relation.isPartOf | Nature communications | |
pubs.issue | 1 | |
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/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/19/20 Starting Cohort | |
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/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Oncogenomics | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/16/17 Starting Cohort | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/19/20 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 11 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Translational Oncogenomics | |
dc.contributor.icrauthor | Woolston, Andrew | |
dc.contributor.icrauthor | Semiannikova, Maria | |
dc.contributor.icrauthor | Spain, Georgia | |
dc.contributor.icrauthor | Challoner, Benjamin | |
dc.contributor.icrauthor | Lise, Stefano | |
dc.contributor.icrauthor | Gerlinger, Marco | |