Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma
<i>BCOR</i> (<i>BCL6</i> 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 <i>ESWR1</i> gene translocation. Due to their s...
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MDPI AG
2023-01-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/15/3/898 |
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| author | Yi-Che Chang Chien Kristóf Madarász Szilvia Lilla Csoma János András Mótyán Hsuan-Ying Huang Gábor Méhes Attila Mokánszki |
| author_facet | Yi-Che Chang Chien Kristóf Madarász Szilvia Lilla Csoma János András Mótyán Hsuan-Ying Huang Gábor Méhes Attila Mokánszki |
| author_sort | Yi-Che Chang Chien |
| collection | DOAJ |
| description | <i>BCOR</i> (<i>BCL6</i> 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 <i>ESWR1</i> gene translocation. Due to their similar morphology and histopathological features, diagnosis is challenging. The most common genetic aberrations are <i>BCOR-CCNB3</i> fusion and <i>BCOR</i> internal tandem duplication (ITD). Recently, various new fusion partners of <i>BCOR</i> have been documented, such as <i>MAML3</i>, <i>ZC3H7B</i>, <i>RGAG1</i>, and <i>KMT2D</i>, 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 <i>BCOR-CLGN</i> (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. |
| first_indexed | 2024-03-11T09:50:21Z |
| format | Article |
| id | doaj.art-b1f4fdfadc06484b894c4c38dc6e35eb |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-11T09:50:21Z |
| publishDate | 2023-01-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-b1f4fdfadc06484b894c4c38dc6e35eb2023-11-16T16:18:49ZengMDPI AGCancers2072-66942023-01-0115389810.3390/cancers15030898Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged SarcomaYi-Che Chang Chien0Kristóf Madarász1Szilvia Lilla Csoma2János András Mótyán3Hsuan-Ying Huang4Gábor Méhes5Attila Mokánszki6Department of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Biochemistry and Molecular Biology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Kaohsiung 83301, TaiwanDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, HungaryDepartment of Pathology, Faculty of Medicine, University of Debrecen, H-4032 Debrecen, Hungary<i>BCOR</i> (<i>BCL6</i> 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 <i>ESWR1</i> gene translocation. Due to their similar morphology and histopathological features, diagnosis is challenging. The most common genetic aberrations are <i>BCOR-CCNB3</i> fusion and <i>BCOR</i> internal tandem duplication (ITD). Recently, various new fusion partners of <i>BCOR</i> have been documented, such as <i>MAML3</i>, <i>ZC3H7B</i>, <i>RGAG1</i>, and <i>KMT2D</i>, 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 <i>BCOR-CLGN</i> (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.https://www.mdpi.com/2072-6694/15/3/898<i>BCOR</i>-rearranged sarcomaimmunohistochemistry<i>BCOR-CLGN</i> gene fusionnext-generation sequencingin silico protein analysiscalmegin |
| spellingShingle | Yi-Che Chang Chien Kristóf Madarász Szilvia Lilla Csoma János András Mótyán Hsuan-Ying Huang Gábor Méhes Attila Mokánszki Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma Cancers <i>BCOR</i>-rearranged sarcoma immunohistochemistry <i>BCOR-CLGN</i> gene fusion next-generation sequencing in silico protein analysis calmegin |
| title | Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma |
| title_full | Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma |
| title_fullStr | Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma |
| title_full_unstemmed | Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma |
| title_short | Molecular Identification and In Silico Protein Analysis of a Novel <i>BCOR-CLGN</i> Gene Fusion in Intrathoracic <i>BCOR</i>-Rearranged Sarcoma |
| title_sort | molecular identification and in silico protein analysis of a novel i bcor clgn i gene fusion in intrathoracic i bcor i rearranged sarcoma |
| topic | <i>BCOR</i>-rearranged sarcoma immunohistochemistry <i>BCOR-CLGN</i> gene fusion next-generation sequencing in silico protein analysis calmegin |
| url | https://www.mdpi.com/2072-6694/15/3/898 |
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