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A novel subtype classification and risk of breast cancer by histone modification profiling

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Abstract

Breast cancer has been classified into several intrinsic molecular subtypes on the basis of genetic and epigenetic factors. However, knowledge about histone modifications that contribute to the classification and development of biologically distinct breast cancer subtypes remains limited. Here we compared the genome-wide binding patterns of H3K4me3 and H3K27me3 between human mammary epithelial cells and three breast cancer cell lines representing the luminal, HER2, and basal subtypes. We characterized thousands of unique binding events as well as bivalent chromatin signatures unique to each cancer subtype, which were involved in different epigenetic regulation programs and signaling pathways in breast cancer progression. Genes linked to the unique histone mark features exhibited subtype-specific expression patterns, both in cancer cell lines and primary tumors, some of which were confirmed by qPCR in our primary cancer samples. Finally, histone mark-based gene classifiers were significantly correlated with relapse-free survival outcomes in patients. In summary, we have provided a valuable resource for the identification of novel biomarkers of subtype classification and clinical prognosis evaluation in breast cancers.

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Acknowledgments

We thank the respective authors for their contributions to generate the sequencing data, as well as all the people who participated in this study and helped us successfully complete the research. This work was supported by the National Natural Science Foundation of China (Grant No. 81372077).

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    Authors and Affiliations

    1. Departmemt of Plastic, Aesthetic and Craniofacial Surgery, The First Affiliated Hospital of Xi’an Jiaotong University, Xi’an, 710061, China

      Xiaohua Chen, Lin He, Xueyuan Yu, Xiangyu Liu & Maoguo Shu

    2. Department of Laboratory Medicine, No.161 Hospital of PLA, Wuhan, 430010, China

      Xiaohua Chen

    3. School of Basic Medical Science, Wuhan University, Wuhan, 430071, China

      Xiaohua Chen & Hanyang Hu

    4. Department of Plastic Surgery, Xijing Hospital, Forth Military Medical University, Xi’an, 710032, China

      Maoguo Shu

    5. Department of Epidemiology and Biostatistics and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

      Rong Zhong

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    1. Xiaohua Chen
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    Xiaohua Chen and Hanyang Hu have contributed equally to this work.

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    Chen, X., Hu, H., He, L. et al. A novel subtype classification and risk of breast cancer by histone modification profiling. Breast Cancer Res Treat 157, 267–279 (2016). https://doi.org/10.1007/s10549-016-3826-8

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