Cell
Volume 171, Issue 4, 2 November 2017, Pages 950-965.e28
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Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

https://doi.org/10.1016/j.cell.2017.10.014Get rights and content
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Highlights

  • Multiplatform genetic analysis of 206 sarcomas of 6 types shows their diversity

  • Sarcomas harbor many more copy-number alterations than most other cancer types

  • Inferred immune microenvironment associates with outcome in multiple sarcoma types

  • Computed histologic nuclear pleomorphism correlates with aneuploidy estimates

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.

Keywords

genomics
immune infiltration
The Cancer Genome Atlas
pleomorphism
DNA methylation
molecular subtype
dedifferentiated liposarcoma
leiomyosarcoma
undifferentiated pleomorphic sarcoma
myxofibrosarcoma

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Lead Contact (Alexander J. Lazar)