Figure 4.

Genomic and transcript profiles of CRTC1-SS18 positive sarcomas. (A) FISH analysis using an SS18 break-apart probe, showing multiple copies of chromosome 18 carrying the SS18 gene. Most cells were tetrasomic or greater for the SS18 locus on chromosome 19. In case 1, the translocation was balanced (presence of red dots) whereas in case 2 the translocation was unbalanced (the red signal is lost while the green signal remains). (B) Array-comparative genomic hybridization (aCGH) profiles. Case 1 presented a diploid genome with the loss of chromosome 1, 3p, 9, part of 11q, 17p, 18 and 22, together with gains on chromosomes 3q, 5, 6, 7, 9, 10, 11, 16, 17, 20 and 21. The region around the SS18 gene on chromosome 18 was focally gained while the CRTC1 gene locus was normal, which is in accordance with a balanced translocation. Case 2 presented a tetraploid genome with the loss of one copy of chromosomes 1, 3, 13, 14, 17, 21 and 22 and with homozygous deletion of chromosome region 17q22, impacting the MBTD1, UTP18 and CA10 genes. The 5’ region of SS18 (on the minus strand) and 3’ region of CRTC1 (on the plus strand) were lost, in accordance with an unbalanced translocation. (C) Hierarchical clustering of RNAseq data placed the two CRTC1-SS18 cases close to EWSR1-CREB1-positive tumours. (D) NTRK1 expression from RNAseq data. AFH/ PPMS: Angiomatoid fibrous histiocytoma / Primary pulmonary myxoid sarcoma; CCCS: cutaneous clear cell sarcomas; CM-CT: Cutaneous Melanocytomas with CRTC1-TRIM11 fusion; BCR: BCOR-Rearranged sarcomas; CD4: CIC-DUX4 sarcomas; EwS: Ewing Sarcomas; SS: synovial sarcomas.