期刊
SCIENTIFIC REPORTS
卷 8, 期 -, 页码 -出版社
NATURE RESEARCH
DOI: 10.1038/s41598-018-29992-5
关键词
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资金
- PhRMA Foundation [2007RSGl9572]
- National Institute of General Medical Sciences [R01 GM081686, R01 GM0866465]
- Eli AMP
- Edythe Broad Center of Regenerative Medicine AMP
- Stem Cell Research
- Iris Cantor Women's Health Center/UCLA CTSI NIH [UL1TR000124]
- Leukemia Lymphoma Society
- Broad Stem Cell Research Center
- UCLA SPORE in Prostate Cancer (National Cancer Institute of the National Institutes of Health) [P50CA092131]
- Cancer Research Institute
Triple-negative breast cancers (TNBC) lack estrogen and progesterone receptors and HER2 amplification, and are resistant to therapies that target these receptors. Tumors from TNBC patients are heterogeneous based on genetic variations, tumor histology, and clinical outcomes. We used high throughput genomic data for TNBC patients (n = 137) from TCGA to characterize inter-tumor heterogeneity. Similarity network fusion (SNF)-based integrative clustering combining gene expression, miRNA expression, and copy number variation, revealed three distinct patient clusters. Integrating multiple types of data resulted in more distinct clusters than analyses with a single datatype. Whereas most TNBCs are classified by PAM50 as basal subtype, one of the clusters was enriched in the non-basal PAM50 subtypes, exhibited more aggressive clinical features and had a distinctive signature of oncogenic mutations, miRNAs and expressed genes. Our analyses provide a new classification scheme for TNBC based on multiple omics datasets and provide insight into molecular features that underlie TNBC heterogeneity.
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