Undifferentiated sarcomas develop through distinct evolutionary pathways
More about Open Access at the CrickAuthors list
Christopher D Steele Maxime Tarabichi Dahmane Oukrif Amy P Webster Hongtao Ye Matthew Fittall Patrick Lombard Iñigo 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 PillayAbstract
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.
Full text links
Publisher website (DOI) 10.1016/j.ccell.2019.02.002
Figshare View on figshare
Europe PubMed Central 30889380
Pubmed 30889380
Keywords
Related topics
Type of publication
