Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies
Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies
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三阴性乳腺癌的基因组和转录组景观：亚型和治疗策略
DOI：
10.1016/j.ccell.2019.02.001
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发表时间：
2019-03-18
期刊：
影响因子：
50.3
通讯作者：
Shao, Zhi-Ming
中科院分区：
文献类型：
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作者：
Jiang, Yi-Zhou;Ma, Ding;Shao, Zhi-Ming
我们全面分析了465例原发性三脾阴性乳腺癌（TNBC）的临床、基因组和转录组学数据。PIK3CA突变和染色体22q11的拷贝数增加在我们的中国队列中比在癌症基因组图谱中更常见。我们将TNBC分为四种基于转录组的亚型：（1）管腔雄激素受体（LAR），（2）免疫调节型，（3）基底样免疫抑制型，和（4）间充质样型。在每种亚型中鉴定推定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丢失。本文提供的TNBC的综合概况将作为进一步促进对TNBC的理解和精确治疗的参考。
We comprehensively analyzed clinical, genomic, and transcriptomic data of a cohort of 465 primary triplenegative 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.