作者
Christopher D Steele, Maxime Tarabichi, Dahmane Oukrif, Amy P Webster, Hongtao Ye, Matthew Fittall, Patrick Lombard, Inigo Martincorena, Patrick S Tarpey, Grace Collord, Kerstin Haase, Sandra J Strauss, Fitim Berisha, Heli Vaikkinen, Pawan Dhami, Marnix Jansen, Sam Behjati, M Fernanda Amary, Roberto Tirabosco, Andrew Feber, Peter J Campbell, Ludmil B Alexandrov, Peter Van Loo, Adrienne M Flanagan, Nischalan Pillay
发表日期
2019/3/18
期刊
Cancer Cell
卷号
35
期号
3
页码范围
441-456. e8
出版商
Elsevier
简介
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 timing models 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.
引用总数
20192020202120222023202461520261910
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