Molecular Identification and In Silico Protein Analysis of a Novel BCOR-CLGN Gene Fusion in Intrathoracic BCOR -Rearranged Sarcoma.

Simple Summary: BCOR (BCL6 corepressor)-rearranged sarcoma (BRS) is a rare sarcoma entity with a predominantly BCOR-CCNB3 fusion. In this paper, we present an index case of BRS with a novel BCOR-CLGN (calmegin) gene fusion that was first identified by next-generation sequencing and then verified by Sanger sequencing. We also carried out in silico protein analysis to demonstrate the 3D structure of the chimera protein. We concluded that, due to its heterogeneity, molecular ancillary tests serve as powerful tools to discover such unusual variants. The fusion protein used in the in silico analysis is an appropriate approach to understanding the exact pathogenesis of such a rare variant. BCOR (BCL6 corepressor)-rearranged sarcomas (BRSs) are a heterogeneous group of sarcomas previously classified as part of the group of "atypical Ewing" or "Ewing-like" sarcomas, without the prototypical ESWR1 gene translocation. Due to their similar morphology and histopathological features, diagnosis is challenging. The most common genetic aberrations are BCOR-CCNB3 fusion and BCOR internal tandem duplication (ITD). Recently, various new fusion partners of BCOR have been documented, such as MAML3, ZC3H7B, RGAG1, and KMT2D, further increasing the complexity of such tumor entities, although the molecular pathogenetic mechanism remains to be elucidated. Here, we present an index case of intrathoracic BRS that carried a novel BCOR-CLGN (calmegin) gene fusion, exhibited by a 52-year-old female diagnosed initially by immunohistochemistry due to the positivity of a BCOR stain; the fusion was identified by next-generation sequencing and was confirmed by Sanger sequencing. In silico protein analysis was performed to demonstrate the 3D structure of the chimera protein. The physicochemical properties of the fusion protein sequence were calculated using the ProtParam web-server tool. Our finding further broadens the fusion partner gene spectrum of BRS. Due to the heterogeneity, molecular ancillary tests serve as powerful tools to discover these unusual variants, and an in silico analysis of the fusion protein offers an appropriate approach toward understanding the exact pathogenesis of such a rare variant. [ABSTRACT FROM AUTHOR]