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

2020; Nature Portfolio; Volume: 1; Issue: 2 Linguagem: Inglês

10.1038/s43018-020-0026-6

2662-1347

H. Raza Ali, Hartland W. Jackson, Vito Riccardo Tomaso Zanotelli, Esther Danenberg, Jana Fischer, Helen Bardwell, Elena Provenzano, H. Raza Ali, M. Al Sa’d, Shahar Alon, Samuel Aparício, Giorgia Battistoni, Shankar Balasubramanian, Robert Becker, Bernd Bodenmiller, E. S. Boyden, Dario Bressan, Alejandra Bruna, B. Marcel, Carlos Caldas, Maurizio Callari, Ian G. Cannell, Helen Casbolt, N. Chornay, Yi Cui, A. Dariush, K. Dinh, A. Emenari, Y. Eyal-Lubling, Jean Fan, Edward A. Fisher, E. A. González-Solares, C. Gónzalez-Fernández, Daniel Goodwin, Wendy Greenwood, Francesco Grimaldi, Gregory J. Hannon, Owen Harris, Shelley Harris, Cristina Jauset, Johanna A. Joyce, Emmanouil D. Karagiannis, Tatjana Kovačević, Laura Kuett, Russell Kunes, A. Yoldaş, Dongbing Lai, Emma Laks, Hsuan Lee, M. Lee, Giulia Lerda, Y. Li, Andrew McPherson, Neal L. Millar, Claire M. Mulvey, Fiona Nugent, Ciara H. O’Flanagan, Marta Pàez‐Ribes, I. Pearsall, Fatime Qosaj, Andrew Roth, Oscar M. Rueda, Tamara Ruiz, Kirsty Sawicka, Leonardo A. Sepúlveda, Sohrab P. Shah, Abigail Shea, Anubhav Sinha, Adrian L. Smith, Simon Tavaré, Sandra Tietscher, Ignacio Vázquez-Garćıa, Siegfried Vogl, N. A. Walton, Asmamaw T. Wassie, Spencer S. Watson, Sonja Wild, Elena Williams, Jonas Windhager, C. Xia, Ping Zheng, Xiaowei Zhuang, Oscar M. Rueda, Suet‐Feung Chin, Samuel Aparício, Carlos Caldas, Bernd Bodenmiller,

Cell Image Analysis Techniques

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.