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dc.contributor.authorPoudel, P
dc.contributor.authorNyamundanda, G
dc.contributor.authorPatil, Y
dc.contributor.authorCheang, MCU
dc.contributor.authorSadanandam, A
dc.date.accessioned2019-12-13T14:33:50Z
dc.date.issued2019-01
dc.identifier.citationNPJ breast cancer, 2019, 5 pp. 21 - ?
dc.identifier.issn2374-4677
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/3474
dc.identifier.eissn2374-4677
dc.identifier.doi10.1038/s41523-019-0116-8
dc.description.abstractBreast cancer is a highly heterogeneous disease. Although differences between intrinsic breast cancer subtypes have been well studied, heterogeneity within each subtype, especially luminal-A cancers, requires further interrogation to personalize disease management. Here, we applied well-characterized and cancer-associated heterocellular signatures representing stem, mesenchymal, stromal, immune, and epithelial cell types to breast cancer. This analysis stratified the luminal-A breast cancer samples into five subtypes with a majority of them enriched for a subtype (stem-like) that has increased stem and stromal cell gene signatures, representing potential luminal progenitor origin. The enrichment of immune checkpoint genes and other immune cell types in two (including stem-like) of the five heterocellular subtypes of luminal-A tumors suggest their potential response to immunotherapy. These immune-enriched subtypes of luminal-A tumors (containing only estrogen receptor positive samples) showed good or intermediate prognosis along with the two other differentiated subtypes as assessed using recurrence-free and distant metastasis-free patient survival outcomes. On the other hand, a partially differentiated subtype of luminal-A breast cancer with transit-amplifying colon-crypt characteristics showed poor prognosis. Furthermore, published luminal-A subtypes associated with specific somatic copy number alterations and mutations shared similar cellular and mutational characteristics to colorectal cancer subtypes where the heterocellular signatures were derived. These heterocellular subtypes reveal transcriptome and cell-type based heterogeneity of luminal-A and other breast cancer subtypes that may be useful for additional understanding of the cancer type and potential patient stratification and personalized medicine.
dc.formatElectronic-eCollection
dc.format.extent21 - ?
dc.languageeng
dc.language.isoeng
dc.rights.urihttps://creativecommons.org/licenses/by/4.0
dc.titleHeterocellular gene signatures reveal luminal-A breast cancer heterogeneity and differential therapeutic responses.
dc.typeJournal Article
dcterms.dateAccepted2019-06-25
rioxxterms.versionofrecord10.1038/s41523-019-0116-8
rioxxterms.licenseref.urihttps://creativecommons.org/licenses/by/4.0
rioxxterms.licenseref.startdate2019-01
rioxxterms.typeJournal Article/Review
dc.relation.isPartOfNPJ breast cancer
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
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/Clinical Studies
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Clinical Studies/Genomic Analysis – Clinical Trials
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology
pubs.organisational-group/ICR/Primary Group/ICR Divisions/Molecular Pathology/Systems and Precision Cancer Medicine
pubs.publication-statusPublished
pubs.volume5
pubs.embargo.termsNot known
icr.researchteamGenomic Analysis – Clinical Trialsen_US
icr.researchteamSystems and Precision Cancer Medicineen_US
dc.contributor.icrauthorSadanandam, Angurajen
dc.contributor.icrauthorCheang, Chonen


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