dc.contributor.author | Heindl, A | |
dc.contributor.author | Khan, AM | |
dc.contributor.author | Rodrigues, DN | |
dc.contributor.author | Eason, K | |
dc.contributor.author | Sadanandam, A | |
dc.contributor.author | Orbegoso, C | |
dc.contributor.author | Punta, M | |
dc.contributor.author | Sottoriva, A | |
dc.contributor.author | Lise, S | |
dc.contributor.author | Banerjee, S | |
dc.contributor.author | Yuan, Y | |
dc.date.accessioned | 2018-11-20T12:49:15Z | |
dc.date.issued | 2018-09-25 | |
dc.identifier.citation | Nature communications, 2018, 9 (1), pp. 3917 - ? | |
dc.identifier.issn | 2041-1723 | |
dc.identifier.uri | https://repository.icr.ac.uk/handle/internal/2950 | |
dc.identifier.eissn | 2041-1723 | |
dc.identifier.doi | 10.1038/s41467-018-06130-3 | |
dc.description.abstract | How tumor microenvironmental forces shape plasticity of cancer cell morphology is poorly understood. Here, we conduct automated histology image and spatial statistical analyses in 514 high grade serous ovarian samples to define cancer morphological diversification within the spatial context of the microenvironment. Tumor spatial zones, where cancer cell nuclei diversify in shape, are mapped in each tumor. Integration of this spatially explicit analysis with omics and clinical data reveals a relationship between morphological diversification and the dysregulation of DNA repair, loss of nuclear integrity, and increased disease mortality. Within the Immunoreactive subtype, spatial analysis further reveals significantly lower lymphocytic infiltration within diversified zones compared with other tumor zones, suggesting that even immune-hot tumors contain cells capable of immune escape. Our findings support a model whereby a subpopulation of morphologically plastic cancer cells with dysregulated DNA repair promotes ovarian cancer progression through positive selection by immune evasion. | |
dc.format | Electronic | |
dc.format.extent | 3917 - ? | |
dc.language | eng | |
dc.language.iso | eng | |
dc.publisher | NATURE RESEARCH | |
dc.rights.uri | https://creativecommons.org/licenses/by/4.0 | |
dc.subject | Lymphocytes | |
dc.subject | Stromal Cells | |
dc.subject | Humans | |
dc.subject | Ovarian Neoplasms | |
dc.subject | BRCA1 Protein | |
dc.subject | Prognosis | |
dc.subject | Gene Expression Profiling | |
dc.subject | Gene Expression Regulation, Neoplastic | |
dc.subject | Adult | |
dc.subject | Aged | |
dc.subject | Aged, 80 and over | |
dc.subject | Middle Aged | |
dc.subject | Female | |
dc.subject | Kaplan-Meier Estimate | |
dc.subject | Tumor Microenvironment | |
dc.subject | Cell Plasticity | |
dc.title | Microenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity. | |
dc.type | Journal Article | |
dcterms.dateAccepted | 2018-08-15 | |
rioxxterms.versionofrecord | 10.1038/s41467-018-06130-3 | |
rioxxterms.licenseref.uri | https://creativecommons.org/licenses/by/4.0 | |
rioxxterms.licenseref.startdate | 2018-09-25 | |
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/Computational Pathology & Integrated Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
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/Computational Pathology & Integrated Genomics | |
pubs.organisational-group | /ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine | |
pubs.organisational-group | /ICR/Primary Group/Royal Marsden Clinical Units | |
pubs.publication-status | Published | |
pubs.volume | 9 | |
pubs.embargo.terms | Not known | |
icr.researchteam | Computational Pathology & Integrated Genomics | |
icr.researchteam | Systems and Precision Cancer Medicine | |
dc.contributor.icrauthor | Eason, Katherine | |
dc.contributor.icrauthor | Sottoriva, Andrea | |
dc.contributor.icrauthor | Lise, Stefano | |
dc.contributor.icrauthor | Yuan, Yinyin | |