Comprehensive and Integrated Genomic Characterization of Adult Soft Tissue Sarcomas

Cell. Volume 171 Issue 4: p950-965, 2 November 2017 10.1016/j.cell.2017.10.014

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.

Data in the GDC

• GDC Manifests
  • Open-Access Data - Download Manifest (17 Files)
  • Controlled-Access Data - Download Manifest (2 Files)

Supplemental Data

• MAF Files
  • Whole exome MAF - genome.wustl.edu_SARC.IlluminaHiSeq_DNASeq_automated.1.5.0.vep.somatic.maf
  • Whole genome MAF - genome.wustl.edu_SARC.IlluminaHiSeq_DNASeq_WGS_PROTECTED.2016-08-11_mmclella_wustl.somatic-wgs-protected.maf.gz
• Data Files
  • Immune infiltration scores - BINDEA_immune_scores_all_data_matrix.xlsx
  • Curated copy number calls by gene - CN_by_genes_pansarc.xlsx
  • RPPA antibodies - RPPA_antibody_list_for_TCGA-SARC_8-4-17.xls
  • Gene fusion analysis results - SARC_264_Fusion_Gene_Profiles.txt
  • SARC Clinical Data - SARC_Clinical_Data_Jan-25-2016_Freeze_Cases_Only.xlsx
  • Sample purity and ploidy table - SARC_purity_ploidy.txt
  • BAM File Freeze List - TCGA-SARC-BAMlist_20171108.tsv
  • Data Freeze List - TCGA_Sarcoma_AWG_FINAL__Freeze_List_9.10.15.xlsx
  • S0. Master Patient Table - SARC_Master_Patient_Table.xlsx
  • S1. Characteristics of patients in the study - tcga_sarc_table_S1_1-27-17_p.xlsx
  • S2. Samples with gain in telomere length as inferred by BIC-guided Gaussian clustering - tcga_sarc_table_S2_7-1-17.docx
  • S3. Discriminative features for iCluster Pan-sarcoma solution - tcga_sarc_table_S3_7-1-17.xlsx
  • S4. CNAs and correlations with mRNA in DDLPS - tcga_sarc_table_S4_7-1-17.xlsx
  • S5. miRNA associated with survival in LMS - tcga_sarc_table_s5_6-16-17-egd_JN.xlsx
  • S6. STLMS samples clustering with ULMS and ULMS samples clustering with STLMS in the iCluster analysis - tcga_sarc_table_S6_7-1-17.docx
  • S7. Genes significantly differentially expressed in STLMS iCluster C1 vs iCluster C2 - tcga_sarc_table_s7_7-1-17.xlsx
  • Telomere length data - TCGA_Sarc_Telomere_Length.xlsx

Additional Resources

• Interactive iCoMut plot in Firebrowse (link is external) The Broad Institute
• Broad Institute FireBrowse portal (link is external) The Broad Institute
• cBioPortal for Cancer Genomics (link is external) Memorial Sloan-Kettering Cancer Center
• TCGA Batch Effects (link is external) MD Anderson Cancer Center
• Regulome Explorer (link is external) Institute for Systems Biology
• Next-Generation Clustered Heat Maps (link is external) MD Anderson Cancer Center