Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, P.R. China.
State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, 2005 Songhu Road, Shanghai 200438, P.R. China; Department of Epidemiology, School of Public Health, Fudan University, Shanghai 200032, P.R. China.
Cancer Cell. 2019 Mar 18;35(3):428-440.e5. doi: 10.1016/j.ccell.2019.02.001. Epub 2019 Mar 7.
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triple-negative breast cancer (TNBC). PIK3CA mutations and copy-number gains of chromosome 22q11 were more frequent in our Chinese cohort than in The Cancer Genome Atlas. We classified TNBCs into four transcriptome-based subtypes: (1) luminal androgen receptor (LAR), (2) immunomodulatory, (3) basal-like immune-suppressed, and (4) mesenchymal-like. Putative therapeutic targets or biomarkers were identified among each subtype. Importantly, the LAR subtype showed more ERBB2 somatic mutations, infrequent mutational signature 3 and frequent CDKN2A loss. The comprehensive profile of TNBCs provided here will serve as a reference to further advance the understanding and precision treatment of TNBC.
我们综合分析了 465 例原发性三阴性乳腺癌（TNBC）患者的临床、基因组和转录组数据。与癌症基因组图谱（The Cancer Genome Atlas）相比，我们的中国队列中 PIK3CA 突变和 22q11 染色体的拷贝数增益更为频繁。我们将 TNBC 分为四个基于转录组的亚型：（1）亮氨酸雄激素受体（LAR），（2）免疫调节型，（3）基底样免疫抑制型，和（4）间充质样型。在每个亚型中都确定了潜在的治疗靶点或生物标志物。重要的是，LAR 亚型显示出更多的 ERBB2 体细胞突变、罕见的突变特征 3 和频繁的 CDKN2A 缺失。这里提供的 TNBC 综合特征将作为进一步深入了解和精准治疗 TNBC 的参考。
