A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.
A single-cell RNA expression atlas of normal, preneoplastic and tumorigenic states in the human breast.
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DOI：
10.15252/embj.2020107333
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发表时间：
2021-06-01
期刊：
影响因子：
--
通讯作者：
Visvader JE
中科院分区：
文献类型：
--
作者：
Pal B;Chen Y;Vaillant F;Capaldo BD;Joyce R;Song X;Bryant VL;Penington JS;Di Stefano L;Tubau Ribera N;Wilcox S;Mann GB;kConFab;Papenfuss AT;Lindeman GJ;Smyth GK;Visvader JE
为了检测不同州乳腺异质性的全球变化，我们确定了340,000个细胞的单细胞转录，包括正常乳腺、癌前病变BRCA1+/-组织、主要乳腺癌亚型、肿瘤对和受累淋巴结。对正常乳房微环境的解释表明，绝经后妇女的间质发生了显着变化。包括雌激素受体(ER)+、HER2+和三阴性乳腺癌在内的34种治疗未获治疗的原发肿瘤的单细胞图谱显示，癌细胞和一组离散的周期细胞之间存在类似的多样性。癌前病变BRCA1+/-组织与肿瘤的转录本突出了免疫微环境的全球变化。在肿瘤免疫格局中，增殖的CD8+T细胞以三阴性和HER2+癌症为特征，而不是ER+肿瘤，而所有亚型都包括循环的肿瘤相关巨噬细胞，因此可能调用不同的免疫治疗靶点。成对的ER+肿瘤和淋巴结的拷贝数分析表明，播种的是遗传上不同的克隆或原发肿瘤细胞大量迁移到腋窝淋巴结。这种患者样本的大规模整合提供了正常和癌变的人类乳房细胞多样性的高分辨率地图。一个大规模的基因表达资源整合了不同的组织样本，揭示了乳腺癌亚型的意外异质性。
To examine global changes in breast heterogeneity across different states, we determined the single‐cell transcriptomes of > 340,000 cells encompassing normal breast, preneoplastic BRCA1 +/– tissue, the major breast cancer subtypes, and pairs of tumors and involved lymph nodes. Elucidation of the normal breast microenvironment revealed striking changes in the stroma of post‐menopausal women. Single‐cell profiling of 34 treatment‐naive primary tumors, including estrogen receptor (ER)+, HER2+, and triple‐negative breast cancers, revealed comparable diversity among cancer cells and a discrete subset of cycling cells. The transcriptomes of preneoplastic BRCA1 +/– tissue versus tumors highlighted global changes in the immune microenvironment. Within the tumor immune landscape, proliferative CD8+ T cells characterized triple‐negative and HER2+ cancers but not ER+ tumors, while all subtypes comprised cycling tumor‐associated macrophages, thus invoking potentially different immunotherapy targets. Copy number analysis of paired ER+ tumors and lymph nodes indicated seeding by genetically distinct clones or mass migration of primary tumor cells into axillary lymph nodes. This large‐scale integration of patient samples provides a high‐resolution map of cell diversity in normal and cancerous human breast. A large‐scale gene expression resource integrates diverse tissue samples and reveals unexpected heterogeneity of breast cancer subtypes.
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影响因子：
4.6
作者：
Bankhead P;Loughrey MB;Fernández JA;Dombrowski Y;McArt DG;Dunne PD;McQuaid S;Gray RT;Murray LJ;Coleman HG;James JA;Salto-Tellez M;Hamilton PW
通讯作者：
Hamilton PW
影响因子：
22.7
作者：
Ali, H. Raza;Jackson, Hartland W.;Bodenmiller, Bernd
通讯作者：
Bodenmiller, Bernd
DOI：
10.1186/bcr921
发表时间：
2004
期刊：
Breast cancer research : BCR
影响因子：
--
作者：
Hankinson SE;Colditz GA;Willett WC
通讯作者：
Willett WC
影响因子：
16.6
作者：
Karaayvaz M;Cristea S;Gillespie SM;Patel AP;Mylvaganam R;Luo CC;Specht MC;Bernstein BE;Michor F;Ellisen LW
通讯作者：
Ellisen LW
影响因子：
64.5
作者：
Kim C;Gao R;Sei E;Brandt R;Hartman J;Hatschek T;Crosetto N;Foukakis T;Navin NE
通讯作者：
Navin NE