Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways
Copyright policy )Undifferentiated Sarcomas Develop through Distinct Evolutionary Pathways
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.
- Uganda Clays (Uganda) Uganda
- University College London United Kingdom
- Université Libre de Bruxelles Belgium
- University of Cambridge United Kingdom
- University of California, San Diego United States
SELECTION, sarcoma, copy-number signatures, Ecology,Evolution & Ethology, Gene Expression Profiling -- methods, Gene Duplication, Human Biology & Physiology, cancer evolution, DNA -- methods, Sarcoma, Sciences bio-médicales et agricoles, Prognosis, CANCER, TUMORS, SOFT-TISSUE SARCOMA, Oncology, Sequence Analysis, Life Sciences & Biomedicine, Genetics & Genomics, PACKAGE, EXPRESSION, 3101 Biochemistry and cell biology, tumor mutational burden, Evolution, Sarcoma -- genetics, mutational signatures, CLASSIFICATION, Article, Evolution, Molecular, 3211 Oncology and carcinogenesis, genomics, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, immuno-oncology, Computational & Systems Biology, Science & Technology, Ploidies, Gene Expression Profiling, Molecular, Cell Biology, Sequence Analysis, DNA, DNA Methylation, Tumour Biology, SUPER-ENHANCERS, FREQUENT MUTATION, Mutation, PATTERNS, 1109 Neurosciences
SELECTION, sarcoma, copy-number signatures, Ecology,Evolution & Ethology, Gene Expression Profiling -- methods, Gene Duplication, Human Biology & Physiology, cancer evolution, DNA -- methods, Sarcoma, Sciences bio-médicales et agricoles, Prognosis, CANCER, TUMORS, SOFT-TISSUE SARCOMA, Oncology, Sequence Analysis, Life Sciences & Biomedicine, Genetics & Genomics, PACKAGE, EXPRESSION, 3101 Biochemistry and cell biology, tumor mutational burden, Evolution, Sarcoma -- genetics, mutational signatures, CLASSIFICATION, Article, Evolution, Molecular, 3211 Oncology and carcinogenesis, genomics, Humans, 1112 Oncology and Carcinogenesis, Oncology & Carcinogenesis, immuno-oncology, Computational & Systems Biology, Science & Technology, Ploidies, Gene Expression Profiling, Molecular, Cell Biology, Sequence Analysis, DNA, DNA Methylation, Tumour Biology, SUPER-ENHANCERS, FREQUENT MUTATION, Mutation, PATTERNS, 1109 Neurosciences
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