Lazar, AJ;
McLellan, MD;
Bailey, MH;
Miller, CA;
Appelbaum, EL;
Cordes, MG;
Fronick, CC;
... Zenklusen, JC; + view all
(2017)
Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas.
Cell
, 171
(4)
950-965.e28.
10.1016/j.cell.2017.10.014.
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Abstract
Summary Sarcomas are a broad family of mesenchymal malignancies exhibiting remarkable histologic diversity. We describe the multi-platform molecular landscape of 206 adult soft tissue sarcomas representing 6 major types. Along with novel insights into the biology of individual sarcoma types, we report three overarching findings: (1) unlike most epithelial malignancies, these sarcomas (excepting synovial sarcoma) are characterized predominantly by copy-number changes, with low mutational loads and only a few genes (TP53, ATRX, RB1) highly recurrently mutated across sarcoma types; (2) within sarcoma types, genomic and regulomic diversity of driver pathways defines molecular subtypes associated with patient outcome; and (3) the immune microenvironment, inferred from DNA methylation and mRNA profiles, associates with outcome and may inform clinical trials of immune checkpoint inhibitors. Overall, this large-scale analysis reveals previously unappreciated sarcoma-type-specific changes in copy number, methylation, RNA, and protein, providing insights into refining sarcoma therapy and relationships to other cancer types.
| Type: | Article |
|---|---|
| Title: | Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas |
| Open access status: | An open access version is available from UCL Discovery |
| DOI: | 10.1016/j.cell.2017.10.014 |
| Publisher version: | https://doi.org/10.1016/j.cell.2017.10.014 |
| Language: | English |
| Additional information: | This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| Keywords: | Science & Technology, Life Sciences & Biomedicine, Biochemistry & Molecular Biology, Cell Biology, SINGLE NUCLEOTIDE POLYMORPHISMS, SMOOTH-MUSCLE DIFFERENTIATION, SOMATIC POINT MUTATIONS, COPY NUMBER ALTERATION, SEQUENCING DATA, HUMAN CANCER, GENE-EXPRESSION, DISCOVERY, CELLS, VALIDATION |
| URI: | https://discovery.ucl.ac.uk/id/eprint/10038678 |
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