Show simple item record

dc.contributor.authorHeindl, Aen_US
dc.contributor.authorKhan, AMen_US
dc.contributor.authorRodrigues, DNen_US
dc.contributor.authorEason, Ken_US
dc.contributor.authorSadanandam, Aen_US
dc.contributor.authorOrbegoso, Cen_US
dc.contributor.authorPunta, Men_US
dc.contributor.authorSottoriva, Aen_US
dc.contributor.authorLise, Sen_US
dc.contributor.authorBanerjee, Sen_US
dc.contributor.authorYuan, Yen_US
dc.coverage.spatialEnglanden_US
dc.date.accessioned2018-11-20T12:49:15Z
dc.date.issued2018-09-25en_US
dc.identifierhttps://www.ncbi.nlm.nih.gov/pubmed/30254278en_US
dc.identifier10.1038/s41467-018-06130-3en_US
dc.identifier.citationNat Commun, 2018, 9 (1), pp. 3917 - ?en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2950
dc.identifier.eissn2041-1723en_US
dc.identifier.doi10.1038/s41467-018-06130-3en_US
dc.description.abstractHow 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.en_US
dc.format.extent3917 - ?en_US
dc.languageengen_US
dc.language.isoengen_US
dc.rights.urihttp://creativecommons.org/licenses/by/4.0/en_US
dc.titleMicroenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.en_US
dc.typeJournal Article
dcterms.dateAccepted2018-08-15en_US
rioxxterms.versionofrecord10.1038/s41467-018-06130-3en_US
rioxxterms.licenseref.startdate2018-09-25en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfNat Communen_US
pubs.issue1en_US
pubs.notesNot knownen_US
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/Evolutionary Genomics & Modelling
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.publication-statusPublished onlineen_US
pubs.volume9en_US
pubs.embargo.termsNot knownen_US
icr.researchteamComputational Pathology & Integrated Genomicsen_US
icr.researchteamEvolutionary Genomics & Modellingen_US
icr.researchteamSystems and Precision Cancer Medicineen_US
dc.contributor.icrauthorYuan, Yinyinen_US
dc.contributor.icrauthorSadanandam, Angurajen_US
dc.contributor.icrauthorSottoriva, Andreaen_US
dc.contributor.icrauthorEason, Katherineen_US


Files in this item

Thumbnail

This item appears in the following Collection(s)

Show simple item record

http://creativecommons.org/licenses/by/4.0/
Except where otherwise noted, this item's license is described as http://creativecommons.org/licenses/by/4.0/