case_images: PMC10601800_01
case_images: Histologic features of CIC-FOXO4 sarcoma. Hematoxylin and eosin stain. a Multinodular subcutaneous mass. b Oval nuclei with molding, cell-cell wrapping and rhabdoid-like cells. c Highly vascular tumor with scattered branching vessels and occasional staghorn-like appearance. d Foci of necrosis and ill formed rosettes (arrow).
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case_images: F1
case_images: Microscopic examination revealed a multinodular, highly cellular neoplasm (Fig. 1a). The neoplastic cells had predominantly oval nuclei with molding and cell-cell wrapping (Fig. 1b). The neoplasm was highly vascular with scattered branching vessels and occasional staghorn-like appearance (Fig. 1c). There was high mitotic activity and foci of necrosis (Fig. 1d); the Ki67 proliferation index was 40%.
case_images: Treatment lines and timeline. A schematic representation of treatment lines. Time is represented horizontally in months. Treatment lines are shown vertically. Every line of therapy was changed due to disease progression under the previous line. L, line; VDC, vincristine, doxorubicin, and cyclophosphamide; DC, dacarbazine and irinotecan; TC, topotecan and cyclophosphamide.
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case_images: F2
case_images: A schematic presentation of the different treatment lines is summarized in Figure 2. We were able to show an in-frame fusion between exon 20 of CIC and exon 2 of FOXO4 (Fig. 2c).
case_images: Establishing CIC-FOXO4 fusion and its suggested protein. a Schematic representation of capicua (CIC) protein. The different domains are shown in rectangles in different colors (text below rectangles, numbers representing the position of the amino acids). The blue arrow represents the part that is included in the suggested protein. The green arrow represents the part that is lost due to the CIC-FOXO4 fusion. The lighting represents the breakpoint by which the translocation occurs. b Schematic presentation of the FOXO4 protein. The different domains are shown in rectangles in different colors (text below rectangles, numbers representing the position of the amino acids). The blue arrow represents the part that is included in the suggested protein. The green arrow represents the part that is lost due to the CIC-FOXO4 fusion. The lighting represents the breakpoint by which the translocation occurs. c Schematic presentation of the suggested fused protein. The blue line represents the part that is derived from the CIC protein and the purple line represents the part that is derived from FOXO4. d Sanger sequencing confirming CIC-FOXO4 fusion. The letters below the peaks represent the different nucleotides. The letters below the horizontal line represent the different amino acids: s - serine; d - aspartate; g - glycine; t - threonine; a - alanine; q - glutamine; k - lysine; l - leucine. ATXN1, Ataxin 1; HMG, high-mobility group; EBS, ERK-binding site; NLS, nuclear localization sequence; FHD, forkhead winged-helix DNA-binding domain; NES, nuclear export sequence; TAD, transactivation domain.
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case_images: PMC10601800_01_cro-2023-0016-0001-533519_F03.jpg
case_images: F3
case_images: As mentioned, FoundationOne Heme  identified a CIC-FOXO4 translocation (Fig. 3a). The chimeric gene can be identified as 5' - CIC (ex. 1-20 UTR NM_015125 - FOXO4 (ex. 2-3 NM_005938) (Fig. 3b).