Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer
Imaging mass cytometry and multiplatform genomics define the phenogenomic landscape of breast cancer
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DOI：
10.1038/s43018-020-0026-6
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发表时间：
2020-02-01
期刊：
影响因子：
22.7
通讯作者：
Bodenmiller, Bernd
中科院分区：
文献类型：
--
作者：
Ali, H. Raza;Jackson, Hartland W.;Bodenmiller, Bernd
基因组改变以不明确的方式塑造细胞表型和肿瘤生态系统的结构。为了研究这些关系，我们使用成像质谱细胞术对来自METABRIC队列的483个肿瘤中的37种蛋白质的表达进行了亚细胞空间分辨率的定量。单细胞分析显示细胞表型跨越上皮，基质和免疫类型。细胞表型和细胞间相互作用的不同组合与乳腺癌的基因组亚型相关。上皮管腔细胞表型分为主要受突变影响的表型和受拷贝数畸变影响的表型。肿瘤生态系统的几个特征，包括细胞邻域，与预后有关，说明了它们的临床相关性。总之，对癌症基因组改变的单细胞表型和空间相关性的系统分析揭示了基因组如何塑造乳腺肿瘤生态系统的组成和结构，并将使人们能够更好地理解基因组改变的表型影响。
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.