Fig. 2: Genetic characteristics of FUS/EWSR1-TFCP2 sarcoma.

a ALK and TERT mRNA expression of tumors from all patients enrolled in the MASTER program until November 21, 2018, and all FUS/EWSR1-TFCP2 cases from the MASTER and INFORM studies (indicated in red). TPM, transcripts per million. b Representative ALK transcript variants (see Supplementary Fig. 2c for the remaining cases). The expression levels of ALK exons are indicated by the depth of coverage (pink, regular exons; blue, upstream exons). The expression levels of splice junctions are indicated by the heights of the arcs connecting the exons. Intragenic deletions lead to exon skipping. c Genomic alterations occurring in three or more FUS/EWSR1-TFCP2 sarcoma samples. Copy-number aberrations were filtered for genes listed in the COSMIC Cancer Gene Census (https://cancer.sanger.ac.uk/census), and only homozygous deletions or amplifications with a total copy number above 2.5-fold base ploidy are shown. SNV, single-nucleotide variant; hom., homozygous; SV, structural variant. d Average copy-number profile across all TFCP2-rearranged cases. avg., average. e Dimensionality reduction (t-SNE) based on the expression levels of 792 transcription factors in 282 RNA-seq samples from 277 sarcoma patients, including 14 samples from 12 TFCP2-rearranged cases. f t-SNE using the 6,000 most variable CpG sites (mvCpGs) from 345 DNA methylation profiles of sarcoma samples analyzed in MASTER (n = 343) and INFORM (n = 2). ESS combines samples assigned to methylation class ESS_HG or ESS_LG. CSA combines samples assigned to methylation class CSA_group_A, CSA_group_B, CSA_MES, or CSA_IDH_group_A. In addition, 11 FUS/EWSR1-TFCP2 cases from nine patients were included, which formed two clusters (TFCP2_1 and TFCP2_2), whereas one sample (HD-12) clustered separately. g Spearman correlation of TFCP2_1 (left panel) and TFCP2_2 (right panel) cases with samples from 19 sarcoma entities based on the same 6000 mvCpGs. Entities are sorted by decreasing correlation from top to bottom. The color code is the same as in f. TFCP2 FUS/EWSR1-TFCP2 sarcoma, RMS_ALV alveolar RMS, RMS_MYOD1 MYOD1-mutant spindle cell/sclerosing RMS, RMS_EMB embryonal RMS, MPNST malignant peripheral nerve sheath tumor, WDLS_DDLS well-differentiated and dedifferentiated liposarcoma, SFT solitary fibrous tumor, CCS clear cell sarcoma, ES epithelioid sarcoma, USARC undifferentiated sarcoma, CHORD chordoma, ASPS alveolar soft part sarcoma, SEF sclerosing epithelioid sarcoma, GIST gastrointestinal stromal tumor, AS angiosarcoma, CSA chondrosarcoma, OS_HG osteosarcoma high-grade, DSRCT desmoplastic small round cell tumor, ESS endometrial stromal sarcoma, EWING Ewing sarcoma, MLS myxoid liposarcoma, SYSA synovial sarcoma.