dc.contributor.author | Kingston, B | |
dc.contributor.author | Cutts, RJ | |
dc.contributor.author | Bye, H | |
dc.contributor.author | Beaney, M | |
dc.contributor.author | Walsh-Crestani, G | |
dc.contributor.author | Hrebien, S | |
dc.contributor.author | Swift, C | |
dc.contributor.author | Kilburn, LS | |
dc.contributor.author | Kernaghan, S | |
dc.contributor.author | Moretti, L | |
dc.contributor.author | Wilkinson, K | |
dc.contributor.author | Wardley, AM | |
dc.contributor.author | Macpherson, IR | |
dc.contributor.author | Baird, RD | |
dc.contributor.author | Roylance, R | |
dc.contributor.author | Reis-Filho, JS | |
dc.contributor.author | Hubank, M | |
dc.contributor.author | Faull, I | |
dc.contributor.author | Banks, KC | |
dc.contributor.author | Lanman, RB | |
dc.contributor.author | Garcia-Murillas, I | |
dc.contributor.author | Bliss, JM | |
dc.contributor.author | Ring, A | |
dc.contributor.author | Turner, NC | |
dc.date.accessioned | 2021-06-11T11:37:28Z | |
dc.date.available | 2021-06-11T11:37:28Z | |
dc.date.issued | 2021-04-23 | |
dc.identifier.citation | Nature communications, 2021, 12 (1), pp. 2423 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/4614 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-021-22605-2 | |
dc.description.abstract | The genomics of advanced breast cancer (ABC) has been described through tumour tissue biopsy sequencing, although these approaches are limited by geographical and temporal heterogeneity. Here we use plasma circulating tumour DNA sequencing to interrogate the genomic profile of ABC in 800 patients in the plasmaMATCH trial. We demonstrate diverse subclonal resistance mutations, including enrichment of HER2 mutations in HER2 positive disease, co-occurring ESR1 and MAP kinase pathway mutations in HR + HER2- disease that associate with poor overall survival (p = 0.0092), and multiple PIK3CA mutations in HR + disease that associate with short progression free survival on fulvestrant (p = 0.0036). The fraction of cancer with a mutation, the clonal dominance of a mutation, varied between genes, and within hotspot mutations of ESR1 and PIK3CA. In ER-positive breast cancer subclonal mutations were enriched in an APOBEC mutational signature, with second hit PIK3CA mutations acquired subclonally and at sites characteristic of APOBEC mutagenesis. This study utilises circulating tumour DNA analysis in a large clinical trial to demonstrate the subclonal diversification of pre-treated advanced breast cancer, identifying distinct mutational processes in advanced ER-positive breast cancer, and novel therapeutic opportunities. | |
dc.format | Electronic | |
dc.format.extent | 2423 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE PORTFOLIO | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Humans | |
dc.subject | Breast Neoplasms | |
dc.subject | Receptor, erbB-2 | |
dc.subject | Receptors, Estrogen | |
dc.subject | Antineoplastic Combined Chemotherapy Protocols | |
dc.subject | Sequence Analysis, DNA | |
dc.subject | Genomics | |
dc.subject | Drug Resistance, Neoplasm | |
dc.subject | Mutation | |
dc.subject | Aged | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Class I Phosphatidylinositol 3-Kinases | |
dc.subject | Biomarkers, Tumor | |
dc.subject | Circulating Tumor DNA | |
dc.subject | Progression-Free Survival | |
dc.title | Genomic profile of advanced breast cancer in circulating tumour DNA. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2021-03-16 | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-021-22605-2 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2021-04-23 | |
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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.) | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/17/18 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/Breast Cancer Research | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Clinical Studies/Clinical Trials & Statistics Unit | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Translational Genomics/Translational Genomics (hon.) | |
pubs.organisational-group | /ICR/Students | |
pubs.organisational-group | /ICR/Students/PhD and MPhil | |
pubs.organisational-group | /ICR/Students/PhD and MPhil/17/18 Starting Cohort | |
pubs.publication-status | Published | |
pubs.volume | 12 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Clinical Trials & Statistics Unit | |
icr.researchteam | Translational Genomics | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Clinical Trials & Statistics Unit | |
icr.researchteam | Translational Genomics | |
dc.contributor.icrauthor | Kingston, Belinda | |
dc.contributor.icrauthor | Cutts, Rosalind | |
dc.contributor.icrauthor | Kilburn, Lucy | |
dc.contributor.icrauthor | Kernaghan, Sarah | |
dc.contributor.icrauthor | Moretti, Laura | |
dc.contributor.icrauthor | Garcia-Murillas, Isaac | |
dc.contributor.icrauthor | Bliss, Judith | |
dc.contributor.icrauthor | Turner, Nicholas | |