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. Author manuscript; available in PMC: 2018 Nov 1.
Published in final edited form as: Am J Surg Pathol. 2017 Nov;41(11):1456–1465. doi: 10.1097/PAS.0000000000000899

Figure 1. Index case of MIFS with a novel TOM1L2-BRAF fusion.

Figure 1

(A) A t(7;17) translocation joining exon 11 of TOM1L2 with exon 9 of BRAF was identified by targeted RNA sequencing and confirmed by RT-PCR. The predicted chimeric protein from the in-frame fusion contains the VHS (Vps27-Hrs-STAM) and GAT (GAA and Tom1) domains of TOM1L2 and the protein kinase domain of BRAF. The N-terminal RBD (Raf-like RAS-binding domain) and C1_1 (Phorbol esters/diacylglycerol binding domain) domains of BRAF with auto-inhibitory functions are replaced. (B) Unbalanced rearrangements of TOM1L2 and BRAF were validated by FISH, showing separate red and green signals with increased copy number of 5′ TOM1L2 (red) and 3′ BRAF (red) (arrows). VGLL3 (3p12.1) amplification was also found by FISH in this case (arrows) (reference probe on 3q12.1–12.2). (C) VGLL3 mRNA expression is up-regulated in the index case (MIFS1) in comparison to other samples, including 2 CIC-rearranged round cell sarcomas (SBRCT1, SBRCT2), 2 synovial sarcomas (SS1, SS2), 1 alveolar rhabdomyosarcoma (RMS), 1 epithelioid hemangioma (EH), 1 soft tissue myoepithelial carcinoma (ME), 1 cellular neurothekeoma (CNT), and 1 low-grade fibromyxoid sarcoma (LGFMS), by same RNA sequencing platform expression analysis.