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dc.contributor.authorHeindl, A
dc.contributor.authorKhan, AM
dc.contributor.authorRodrigues, DN
dc.contributor.authorEason, K
dc.contributor.authorSadanandam, A
dc.contributor.authorOrbegoso, C
dc.contributor.authorPunta, M
dc.contributor.authorSottoriva, A
dc.contributor.authorLise, S
dc.contributor.authorBanerjee, S
dc.contributor.authorYuan, Y
dc.date.accessioned2018-11-20T12:49:15Z
dc.date.issued2018-09-25
dc.identifier.citationNature communications, 2018, 9 (1), pp. 3917 - ?
dc.identifier.issn2041-1723
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2950
dc.identifier.eissn2041-1723
dc.identifier.doi10.1038/s41467-018-06130-3
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.
dc.formatElectronic
dc.format.extent3917 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.subjectLymphocytes
dc.subjectStromal Cells
dc.subjectHumans
dc.subjectOvarian Neoplasms
dc.subjectBRCA1 Protein
dc.subjectPrognosis
dc.subjectGene Expression Profiling
dc.subjectGene Expression Regulation, Neoplastic
dc.subjectAdult
dc.subjectAged
dc.subjectAged, 80 and over
dc.subjectMiddle Aged
dc.subjectFemale
dc.subjectKaplan-Meier Estimate
dc.subjectTumor Microenvironment
dc.subjectCell Plasticity
dc.titleMicroenvironmental niche divergence shapes BRCA1-dysregulated ovarian cancer morphological plasticity.
dc.typeJournal Article
dcterms.dateAccepted2018-08-15
rioxxterms.versionofrecord10.1038/s41467-018-06130-3
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2018-09-25
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNature communications
pubs.issue1
pubs.notesNot 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-statusPublished
pubs.volume9
pubs.embargo.termsNot known
icr.researchteamComputational Pathology & Integrated Genomicsen_US
icr.researchteamSystems and Precision Cancer Medicineen_US
dc.contributor.icrauthorYuan, Yinyinen
dc.contributor.icrauthorEason, Katherineen
dc.contributor.icrauthorSadanandam, Angurajen
dc.contributor.icrauthorSottoriva, Andreaen
dc.contributor.icrauthorBanerjee, Susanaen
dc.contributor.icrauthorLise, Stefanoen


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