Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways

• DOI: 10.1016/j.ccell.2019.02.002
• Publication Date: 2019-03-18T14:40:24Z
• Authors: Christopher D. St...; 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 Pillay
• Keywords: EXPRESSION; SELECTION; sarcoma; tumor mutational burden; Evolution; Sarcoma -- genetics; mutational signatures; copy-number signatures; CLASSIFICATION; Article; Evolution, Molecular; 03 medical and health sciences; Ecology,Evolution & Ethology; Gene Expression Profiling -- methods; Gene Duplication; genomics; Humans; immuno-oncology; Computational & Systems Biology; Human Biology & Physiology; 0303 health sciences; cancer evolution; Science & Technology; Ploidies; Gene Expression Profiling; DNA -- methods; Molecular; Sarcoma; Cell Biology; Sequence Analysis, DNA; Sciences bio-médicales et agricoles; DNA Methylation; Tumour Biology; Prognosis; SUPER-ENHANCERS; CANCER; TUMORS; 3. Good health; FREQUENT MUTATION; SOFT-TISSUE SARCOMA; Oncology; Mutation; PATTERNS; Sequence Analysis; Life Sciences & Biomedicine; Genetics & Genomics; PACKAGE

Undifferentiated sarcomas (USARCs) of adults are diverse, rare, and aggressive soft tissue cancers. Recent sequencing efforts have confirmed that USARCs exhibit one the highest burdens structural aberrations across human cancer. Here, we sought to unravel molecular basis complexity in by integrating DNA sequencing, ploidy analysis, gene expression, methylation profiling. We identified whole genome duplication as a prevalent pernicious force USARC tumorigenesis. Using mathematical deconvolution strategies complex copy-number profiles mutational timing models infer distinct evolutionary pathways these rare In addition, 15% tumors exhibited raised correlated with expression signatures immune infiltration, good prognosis.