Soft‐tissue sarcoma with MN1‐BEND2 fusion: A case report and comparison with astroblastoma

AbstractMN1‐BEND2 is considered as a defining gene fusion of astroblastoma. Herein, we report the first case of soft‐tissue sarcoma with this fusion. The tumor developed in the abdominal wall of an 87‐year‐old woman, and consisted of a striking storiform growth of low‐grade spindle cells admixed with a dense proliferation of oval cells with a higher nuclear atypia and mitotic activity. The sarcoma was immunohistochemically positive for actin but negative for S100 protein, glial fibrillary acidic protein, and Olig2. Targeted RNA sequencing identified an in‐frame MN1 (exon 1)‐BEND2 (exon 11) fusion transcript, which was validated by reverse transcription polymerase chain reaction, Sanger sequencing, and MN1 break‐apart fluorescence in situ hybridization. DNA methylation profiling revealed that the tumor did not match any sarcoma classes based on the DKFZ classifier. Using T‐distributed stochastic neighbor embedding analysis, the sarcoma was plotted close to the provisional class “Sarcoma (malignant peripheral nerve sheath tumor‐like),” despite no phenotypic resemblance. Copy number analysis using methylation data demonstrated losses at 2q, 8p, 9p, 11p, 14q, 19q, and 22q. When compared with a cerebral astroblastoma sample with MN1 (exon 1)‐BEND2 (exon 9) fusion, the sarcoma showed no resemblance in histology, immunophenotype, or DNA methylation profile, although they shared copy number loss at 14q, 19q, and 22q. The present report demonstrated that MN1‐BEND2 is another example of a pleiotropic fusion gene that is shared among different tumor types.