Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

Yi-Zhou Jiang¹, Ding Ma¹, Chen Suo², Jinxiu Shi³, Mengzhu Xue⁴, Xin Hu¹, Yi Xiao¹, Ke-Da Yu¹, Yi-Rong Liu¹, Ying Yu⁵, Yuanting Zheng⁵, Xiangnan Li⁵, Chenhui Zhang³, Pengchen Hu³, Jing Zhang³, Qi Hua³, Jiyang Zhang⁵, Wanwan Hou⁵, Luyao Ren⁵, Ding Bao⁵, Bingying Li⁵, Jingcheng Yang⁵, Ling Yao¹, Wen-Jia Zuo¹, Shen Zhao¹, Yue Gong¹, Yi-Xing Ren¹, Ya-Xin Zhao¹, Yun-Song Yang¹, Zhenmin Niu³, Zhi-Gang Cao¹, Daniel G Stover⁶, Claire Verschraegen⁶, Virginia Kaklamani⁷, Anneleen Daemen⁸, John R Benson⁹, Kazuaki Takabe¹⁰, Fan Bai¹¹, Da-Qiang Li¹, Peng Wang¹², Leming Shi¹³, Wei Huang¹⁴, Zhi-Ming Shao¹⁵

Affiliations

¹ Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, P.R. China.
² 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.
³ Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Industrial Technology Institute (SITI), 250 Bibo Road, Shanghai 201203, P.R. China.
⁴ SARI Center for Stem Cell and Nanomedicine, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, P.R. China.
⁵ State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, 2005 Songhu Road, Shanghai 200438, P.R. China.
⁶ The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
⁷ Division Hematology/Oncology, University of Texas Health Science Center San Antonio, San Antonio, TX 78284, USA.
⁸ Department of Bioinformatics & Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
⁹ Cambridge Breast Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
¹⁰ Division of Breast Surgery, Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
¹¹ Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, P.R. China.
¹² Bio-med Big Data Center, CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P.R. China. Electronic address: wangpeng@picb.ac.cn.
¹³ State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, 2005 Songhu Road, Shanghai 200438, P.R. China. Electronic address: lemingshi@fudan.edu.cn.
¹⁴ Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Industrial Technology Institute (SITI), 250 Bibo Road, Shanghai 201203, P.R. China. Electronic address: huangwei@chgc.sh.cn.
¹⁵ Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, P.R. China. Electronic address: zhimingshao@yahoo.com.

PMID: 30853353
DOI: 10.1016/j.ccell.2019.02.001

Free article

Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

Yi-Zhou Jiang et al. Cancer Cell. 2019.

Free article

. 2019 Mar 18;35(3):428-440.e5.

doi: 10.1016/j.ccell.2019.02.001. Epub 2019 Mar 7.

Authors

Affiliations

¹ Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, P.R. China.
² 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.
³ Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Industrial Technology Institute (SITI), 250 Bibo Road, Shanghai 201203, P.R. China.
⁴ SARI Center for Stem Cell and Nanomedicine, Shanghai Advanced Research Institute, Chinese Academy of Sciences, Shanghai 201210, P.R. China.
⁵ State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, 2005 Songhu Road, Shanghai 200438, P.R. China.
⁶ The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.
⁷ Division Hematology/Oncology, University of Texas Health Science Center San Antonio, San Antonio, TX 78284, USA.
⁸ Department of Bioinformatics & Computational Biology, Genentech Inc., 1 DNA Way, South San Francisco, CA 94080, USA.
⁹ Cambridge Breast Unit, Addenbrooke's Hospital, Hills Road, Cambridge CB2 0QQ, UK.
¹⁰ Division of Breast Surgery, Department of Surgical Oncology, Roswell Park Cancer Institute, Buffalo, NY 14263, USA.
¹¹ Biodynamic Optical Imaging Center (BIOPIC), School of Life Sciences, Peking University, Beijing 100871, P.R. China.
¹² Bio-med Big Data Center, CAS Key Laboratory of Computational Biology, CAS-MPG Partner Institute for Computational Biology, Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, 320 Yueyang Road, Shanghai 200031, P.R. China. Electronic address: wangpeng@picb.ac.cn.
¹³ State Key Laboratory of Genetic Engineering, School of Life Sciences and Human Phenome Institute, Fudan University, 2005 Songhu Road, Shanghai 200438, P.R. China. Electronic address: lemingshi@fudan.edu.cn.
¹⁴ Shanghai-MOST Key Laboratory of Health and Disease Genomics, Chinese National Human Genome Center at Shanghai (CHGC) and Shanghai Industrial Technology Institute (SITI), 250 Bibo Road, Shanghai 201203, P.R. China. Electronic address: huangwei@chgc.sh.cn.
¹⁵ Department of Breast Surgery, Precision Cancer Medicine Center, Fudan University Shanghai Cancer Center, 270 Dong'an Road, Shanghai 200032, P.R. China. Electronic address: zhimingshao@yahoo.com.

PMID: 30853353
DOI: 10.1016/j.ccell.2019.02.001

Abstract

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.

Keywords: genomic; molecular subtype; precision therapies; target; transcriptomic; triple-negative breast cancer.

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Therapeutic Clues from an Integrated Omic Assessment of East Asian Triple Negative Breast Cancers.
Heiser LM, Mills GB, Gray JW. Heiser LM, et al. Cancer Cell. 2019 Mar 18;35(3):341-343. doi: 10.1016/j.ccell.2019.02.012. Cancer Cell. 2019. PMID: 30889376 Free PMC article.

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Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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Genomic and Transcriptomic Landscape of Triple-Negative Breast Cancers: Subtypes and Treatment Strategies

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