期刊
CANCER CELL
卷 35, 期 3, 页码 441-+出版社
CELL PRESS
DOI: 10.1016/j.ccell.2019.02.002
关键词
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资金
- NIH Research, UCLH Biomedical Research Centre
- CRUK UCL Experimental Cancer Center
- BBSRC [BB/R009295/1]
- PCUK [MA-TR15-009]
- Medical Research Council [MR/M025411/1]
- Wellcome Trust [FC001202]
- CRUK
- European Union's Horizon 2020 research and innovation program (Marie Sklodowska-Curie Grant) [747852-SIOMICS]
- Francis Crick Institute from Cancer Research UK [FC001202]
- UK Medical Research Council [FC001202]
- BBSRC [BB/R009295/1] Funding Source: UKRI
- MRC [MR/M025411/1] Funding Source: UKRI
Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one of the highest burdens of structural aberrations across human cancer. Here, we sought to unravel the molecular basis of the structural complexity in USARCs by integrating DNA sequencing, ploidy analysis, gene expression, and methylation profiling. We identified whole genome duplication as a prevalent and pernicious force in USARC tumorigenesis. Using mathematical deconvolution strategies to unravel the complex copy-number profiles and mutational timingmodels we infer distinct evolutionary pathways of these rare cancers. In addition, 15% of tumors exhibited raised mutational burdens that correlated with gene expression signatures of immune infiltration, and good prognosis.
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