dc.contributor.author | Fitzpatrick, A | |
dc.contributor.author | Iravani, M | |
dc.contributor.author | Mills, A | |
dc.contributor.author | Vicente, D | |
dc.contributor.author | Alaguthurai, T | |
dc.contributor.author | Roxanis, I | |
dc.contributor.author | Turner, NC | |
dc.contributor.author | Haider, S | |
dc.contributor.author | Tutt, ANJ | |
dc.contributor.author | Isacke, CM | |
dc.coverage.spatial | England | |
dc.date.accessioned | 2024-02-05T12:13:35Z | |
dc.date.available | 2024-02-05T12:13:35Z | |
dc.date.issued | 2023-11-16 | |
dc.identifier | 7408 | |
dc.identifier | 10.1038/s41467-023-43242-x | |
dc.identifier.citation | Nature Communications, 2023, 14 (1), pp. 7408 - | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/6142 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-023-43242-x | |
dc.identifier.doi | 10.1038/s41467-023-43242-x | |
dc.description.abstract | Breast cancer leptomeningeal metastasis (BCLM), where tumour cells grow along the lining of the brain and spinal cord, is a devastating development for patients. Investigating this metastatic site is hampered by difficulty in accessing tumour material. Here, we utilise cerebrospinal fluid (CSF) cell-free DNA (cfDNA) and CSF disseminated tumour cells (DTCs) to explore the clonal evolution of BCLM and heterogeneity between leptomeningeal and extracranial metastatic sites. Somatic alterations with potential therapeutic actionability were detected in 81% (17/21) of BCLM cases, with 19% detectable in CSF cfDNA only. BCLM was enriched in genomic aberrations in adherens junction and cytoskeletal genes, revealing a lobular-like breast cancer phenotype. CSF DTCs were cultured in 3D to establish BCLM patient-derived organoids, and used for the successful generation of BCLM in vivo models. These data reveal that BCLM possess a unique genomic aberration profile and highlight potential cellular dependencies in this hard-to-treat form of metastatic disease. | |
dc.format | Electronic | |
dc.format.extent | 7408 - | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | Springer Science and Business Media LLC | |
dc.relation.ispartof | Nature Communications | |
dc.rights.uri | http://creativecommons.org/licenses/by/4.0/ | |
dc.subject | Humans | |
dc.subject | Female | |
dc.subject | Breast Neoplasms | |
dc.subject | Meningeal Carcinomatosis | |
dc.subject | Cell-Free Nucleic Acids | |
dc.subject | Genomics | |
dc.title | Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-like phenotype. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2023-11-03 | |
dc.date.updated | 2024-02-05T10:27:24Z | |
rioxxterms.version | VoR | |
rioxxterms.versionofrecord | 10.1038/s41467-023-43242-x | |
rioxxterms.licenseref.startdate | 2023-11-16 | |
rioxxterms.type | Journal Article/Review | |
pubs.author-url | https://www.ncbi.nlm.nih.gov/pubmed/37973922 | |
pubs.issue | 1 | |
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 Cell Biology | |
pubs.organisational-group | ICR/Primary Group/ICR Divisions/Breast Cancer Research/Molecular Oncology | |
pubs.organisational-group | ICR/Students | |
pubs.organisational-group | ICR/Students/PhD and MPhil | |
pubs.organisational-group | ICR/Students/PhD and MPhil/15/16 Starting Cohort | |
pubs.publication-status | Published online | |
pubs.publisher-url | http://dx.doi.org/10.1038/s41467-023-43242-x | |
pubs.volume | 14 | |
icr.researchteam | Molecular Cell Biology | |
icr.researchteam | Molecular Oncology | |
icr.researchteam | Directorate Breast Canc | |
dc.contributor.icrauthor | Fitzpatrick, Amanda | |
dc.contributor.icrauthor | Iravani, Marjan | |
dc.contributor.icrauthor | Turner, Nicholas | |
dc.contributor.icrauthor | Haider, Syed | |
dc.contributor.icrauthor | Tutt, Andrew | |
dc.contributor.icrauthor | Isacke, Clare | |
icr.provenance | Deposited by Ms Alex Carroll (impersonating Prof Andrew Tutt) on 2024-02-05. Deposit type is initial. No. of files: 1. Files: Genomic profiling and pre-clinical modelling of breast cancer leptomeningeal metastasis reveals acquisition of a lobular-lik.pdf | |