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RAF1-rearranged spindle cell tumour: report of two additional cases with identification of a novel FMR1-RAF1 fusion

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Abstract

A subset of spindle cell tumours have been recently identified to harbor recurrent fusion genes, involving NTRK1/2/3, BRAF, RAF1, and RET. The precise classification of these fusion-positive tumours relies essentially on genomic profiling. Herein, we present our experience with two cases of spindle cell tumour which showed RAF1 rearrangement. Both tumours occurred in children with one in the left cheek (case 1) and the other one in the left buttock (case 2). Histologically, case 1 was a low-grade neoplasm characterized by uniform ovoid to short spindle cells showing “patternless” architecture with stromal hyalinization. Case 2 had an overtly malignant phenotype composed of long intersecting fascicles with increased cellularity and mitotic activity. By immunohistochemistry, tumour cells in case 1 showed co-expression of CD34 and S100 protein whereas in case 2 there was only focal staining of CD34 with no expression of S100 protein. Fluorescence in situ hybridization tests using NTRK1/2/3 (case 1 and case 2), ETV6, SS18, BRAF, ROS1, and ALK (case 2) break-apart probes were performed but yielded negative results. Subsequent next-generation sequencing (NGS) demonstrated PDZRN3-RAF1 fusion in case 1 and FMR1-RAF1 fusion in case 2, respectively, which were confirmed by FISH using RAF1 break-apart probe. This study further emphasizes the importance of molecular diagnostics in fusion-positive spindle cell tumours. In addition, we expand the genetic spectrum of RAF1-rearranged spindle cell tumour by describing a novel FMR1-RAF1 fusion gene.

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Acknowledgements

The authors would thank Dr. Xiaoyan Zhou of the Department of Pathology of Fudan University Shanghai Cancer Center and Donglin Chen of the OrigiMed Co. for assistance in NGS analysis, and Shaoyu Chen of Guangzhou LBP Medicine Science & Technology Co., Ltd. for the FISH analysis.

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Authors and Affiliations

  1. Department of Pathology, Tongji Hospital, School of Medicine, Tongji University, 389 Xin Cun Street, Shanghai, 200065, China

    Tingting Zhang, Xianghua Yi & Peipei Zhu

  2. Department of Pathology, Shanghai Children’s Hospital, Shanghai Jiao Tong University, Shanghai, China

    Qingyu Wang

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  1. Tingting Zhang
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Contributions

Tingting Zhang, Qingyu Wang, and Peipei Zhu: Project planning, slide review, data gathering, data analysis, literature review, and manuscript writing.

Peipei Zhu and Xianghua Yi: Slide review and manuscript proofreading

Not applicable, because this article does not contain any studies with human or animal subjects.

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Correspondence to Peipei Zhu.

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Drs. Zhang and Wang contributed equally in the study and thus be considered as co-first authors.

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Zhang, T., Wang, Q., Yi, X. et al. RAF1-rearranged spindle cell tumour: report of two additional cases with identification of a novel FMR1-RAF1 fusion. Virchows Arch 479, 1245–1253 (2021). https://doi.org/10.1007/s00428-021-03178-3

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  • DOI: https://doi.org/10.1007/s00428-021-03178-3

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