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Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer | Nature Cancer
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Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cell–cell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations. Bodenmiller and colleagues pair imaging mass cytometry with data from the METABRIC cohort to define single-cell phenotypic and genomic features of breast cancer with spatial context, finding associations with breast cancer subtypes and prognosis.
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nature portfolio journals privacy policy nature portfolio received research grants advertising social media european research council language reprints cancer research uk gene-expression-based retrospective study suet-feung chin processed single-cell data data-driven phenotypic dissection illumina bead-based data cancer research structured tumor-immune microenvironment publishing agreement pan-tumor genomic biomarkers single-linkage hierarchical clustering high-throughput molecular profiling cd8+ t-cell infiltration calculating exact p-values european genome–phenome archive hypoxia-mediated immune escape nature+ nature nature 406 nature 486 nature 534 nature 497 nature 567 nature 475 nature 481 sided kruskal-wallis tests accepted manuscript version permissions genome-driven integrated classification spatial genomics maps springerlink instant access single-cell phenotypic research curated clinical data cell-cell interactions identified phenograph-assigned cell types luminal breast cancer cell-cell interaction enrichment single-cell atlas conducted data analysis processed genomic data
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description:Genomic alterations shape cell phenotypes and the structure of tumor ecosystems in poorly defined ways. To investigate these relationships, we used imaging mass cytometry to quantify the expression of 37 proteins with subcellular spatial resolution in 483 tumors from the METABRIC cohort. Single-cell analysis revealed cell phenotypes spanning epithelial, stromal and immune types. Distinct combinations of cell phenotypes and cellâcell interactions were associated with genomic subtypes of breast cancer. Epithelial luminal cell phenotypes separated into those predominantly impacted by mutations and those affected by copy number aberrations. Several features of tumor ecosystems, including cellular neighborhoods, were linked to prognosis, illustrating their clinical relevance. In summary, systematic analysis of single-cell phenotypic and spatial correlates of genomic alterations in cancer revealed how genomes shape both the composition and architecture of breast tumor ecosystems and will enable greater understanding of the phenotypic impact of genomic alterations. Bodenmiller and colleagues pair imaging mass cytometry with data from the METABRIC cohort to define single-cell phenotypic and genomic features of breast cancer with spatial context, finding associations with breast cancer subtypes and prognosis.
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