Identification of a novel SH3PXD2B::FER fusion in a case of plexiform myofibroblastic tumor and review of the literature

• Published in: Genes chromosomes & cancer 2024-02, Vol.63 (2), p.e23224-n/a
• Main Authors: Vallese, Silvia, Tancredi, Chantal, Giovannoni, Isabella, Diociaiuti, Andrea, Stracuzzi, Alessandra, Rossi, Sabrina, Alaggio, Rita, Barresi, Sabina
• Format: Article
• Language: English
• Subjects: CD34 antigen; Child; Desmin; Epidermal growth factor receptors; Female; FER gene; Fusion protein; fusion transcript; Humans; Kinases; Literature reviews; Molecular modelling; Neoplasms, Muscle Tissue - genetics; Neoplasms, Muscle Tissue - pathology; Oncogene Proteins, Fusion - genetics; plexiform myofibroblastic tumor; Protein-Tyrosine Kinases - genetics; Protein-Tyrosine Kinases - metabolism; Tumorigenesis; Tumors; tyrosine‐protein kinase
• ISSN: 1045-2257; 1098-2264; 1098-2264
• DOI: 10.1002/gcc.23224

Fibroblastic/myofibroblastic tumors encompass a wide spectrum of lesions. Among them, plexiform myofibroblastoma (PM) represents a rare and distinctive entity recently described as mostly occurring in children and with a favorable prognosis. Histologically, PM shows SMA, CD34, and desmin expression in most cases, while it is negative for β‐catenin and S100. To date, the molecular mechanisms underlying PM tumorigenesis remain largely unknown. Herein, we describe a 7‐year‐old girl with a myofibroblastic lesion with plexiform features arising in the right deltoid region. The tumor proved positive for SMA staining, in absence of desmin, CD34, S100, and EMA expression. RNAseq analysis revealed a novel in‐frame SH3PXD2B::FER fusion gene. The FER gene encodes a cytoplasmic tyrosine kinase which is implicated in several biologically aggressive tumors, where it is overexpressed and associated with EGFR recycling and stabilization. In our case, immunohistochemical analysis revealed a strong positivity for EGFR indicating an upregulation of EGFR transcription that might correlate with the novel chimeric protein involving the FER kinase domain. To our knowledge, the SH3PXD2B::FER fusion has never been reported previously. Whether the current case represents an example of a plexiform myofibroblastic tumor or a distinct tumor entity remains to be determined.