Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer

被引：198

作者：

Ali, H. Raza ^{[1
,2
]}

Jackson, Hartland W. ^{[1
]}

Zanotelli, Vito R. T. ^{[1
]}

Danenberg, Esther ^{[1
]}

Fischer, Jana R. ^{[1
]}

Bardwell, Helen ^{[2
]}

Provenzano, Elena ^{[3
,4
]}

Rueda, Oscar M. ^{[2
]}

Chin, Suet-Feung ^{[2
]}

Aparicio, Samuel ^{[5
]}

Caldas, Carlos ^{[2
,3
,4
]}

Bodenmiller, Bernd ^{[1
]}

机构：

[1] Univ Zurich, Dept Quantitat Biomed, Zurich, Switzerland

[2] Univ Cambridge, CRUK Cambridge Inst, Cambridge, England

[3] Cambridge Univ Hosp NHS Fdn Trust, Addenbrookes Hosp, Cambridge Breast Unit, Cambridge, England

[4] NIHR Cambridge Biomed Res Ctr, Cambridge, England

[5] British Columbia Canc Res Ctr, Mol Oncol, Vancouver, BC, Canada

来源：

NATURE CANCER | 2020年 / 1卷 / 02期

基金：

欧洲研究理事会;

关键词：

SUBCELLULAR RESOLUTION; FIBROBLASTS; HYPOXIA; CLASSIFICATION; HETEROGENEITY; EXPRESSION; DISCOVERY; REVEALS; PACKAGE;

D O I：

10.1038/s43018-020-0026-6

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

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.

引用

页码：163 / +

页数：30

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