CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors
Abstract The fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors introduced the new tumor type CNS tumor with BCOR internal tandem duplication (ITD), characterized by a distinct DNA methylation profile and peculiar histopathological features, in...
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| Format: | Article |
| Language: | English |
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BMC
2024-01-01
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| Series: | Acta Neuropathologica Communications |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s40478-024-01726-x |
| _version_ | 1797355450049495040 |
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| author | Valeria Barresi Antonello Cardoni Evelina Miele Lucia Pedace Barbara Masotto Claudia Nardini Sabina Barresi Sabrina Rossi |
| author_facet | Valeria Barresi Antonello Cardoni Evelina Miele Lucia Pedace Barbara Masotto Claudia Nardini Sabina Barresi Sabrina Rossi |
| author_sort | Valeria Barresi |
| collection | DOAJ |
| description | Abstract The fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors introduced the new tumor type CNS tumor with BCOR internal tandem duplication (ITD), characterized by a distinct DNA methylation profile and peculiar histopathological features, including a circumscribed growth pattern, ependymoma-like perivascular pseudorosettes, microcystic pattern, absent or focal GFAP immunostaining, OLIG2 positivity, and BCOR immunoreactivity. We describe a rare case of a CNS tumor in a 45-year-old man with histopathological and immunohistochemical features overlapping the CNS tumor with BCOR internal tandem duplication (ITD) but lacking BCOR immunostaining and BCOR ITD. Instead, the tumor showed CREBBP::BCORL1 fusion and pathogenic mutations in BCOR and CREBBP, along with a DNA methylation profile matching the “CNS tumor with EP300:BCOR(L1) fusion” methylation class. Two CNS tumors with fusions between CREBBP, or its paralog EP300, and BCORL1, and approximately twenty CNS tumors with CREBBP/EP300::BCOR fusions have been reported to date. They exhibited similar ependymoma-like features or a microcystic pattern, along with focal or absent GFAP immunostaining, and shared the same DNA methylation profile. Given their morphological and epigenetic similarities, circumscribed CNS tumors with EP300/CREBBP::BCOR(L1) fusions and CNS tumors with BCOR ITD may represent variants of the same tumor type. The ependymoma-like aspect coupled with the lack of diffuse GFAP immunostaining and the presence of OLIG2 positivity are useful clues for recognizing these tumors in histopathological practice. The diagnosis should be confirmed after testing for BCOR(L1) gene fusions and BCOR ITD. |
| first_indexed | 2024-03-08T14:11:24Z |
| format | Article |
| id | doaj.art-a146378fe4204cd8b54ed7a8eb6ec363 |
| institution | Directory Open Access Journal |
| issn | 2051-5960 |
| language | English |
| last_indexed | 2024-03-08T14:11:24Z |
| publishDate | 2024-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj.art-a146378fe4204cd8b54ed7a8eb6ec3632024-01-14T12:42:12ZengBMCActa Neuropathologica Communications2051-59602024-01-011211710.1186/s40478-024-01726-xCNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumorsValeria Barresi0Antonello Cardoni1Evelina Miele2Lucia Pedace3Barbara Masotto4Claudia Nardini5Sabina Barresi6Sabrina Rossi7Department of Diagnostics and Public Health, University of VeronaPathology Unit, Bambino Gesù Children’s Hospital, IRCCSOncohematology Research Area, Genetics and Epigenetics of tumors, IRCCS Bambino Gesù Children’s HospitalOncohematology Research Area, Genetics and Epigenetics of tumors, IRCCS Bambino Gesù Children’s HospitalUnit of Cranial Posterior Fossa Surgery, University and Hospital Trust of VeronaOncohematology Research Area, Genetics and Epigenetics of tumors, IRCCS Bambino Gesù Children’s HospitalOncohematology Research Area, Genetics and Epigenetics of tumors, IRCCS Bambino Gesù Children’s HospitalPathology Unit, Bambino Gesù Children’s Hospital, IRCCSAbstract The fifth edition of the World Health Organization (WHO) classification of central nervous system (CNS) tumors introduced the new tumor type CNS tumor with BCOR internal tandem duplication (ITD), characterized by a distinct DNA methylation profile and peculiar histopathological features, including a circumscribed growth pattern, ependymoma-like perivascular pseudorosettes, microcystic pattern, absent or focal GFAP immunostaining, OLIG2 positivity, and BCOR immunoreactivity. We describe a rare case of a CNS tumor in a 45-year-old man with histopathological and immunohistochemical features overlapping the CNS tumor with BCOR internal tandem duplication (ITD) but lacking BCOR immunostaining and BCOR ITD. Instead, the tumor showed CREBBP::BCORL1 fusion and pathogenic mutations in BCOR and CREBBP, along with a DNA methylation profile matching the “CNS tumor with EP300:BCOR(L1) fusion” methylation class. Two CNS tumors with fusions between CREBBP, or its paralog EP300, and BCORL1, and approximately twenty CNS tumors with CREBBP/EP300::BCOR fusions have been reported to date. They exhibited similar ependymoma-like features or a microcystic pattern, along with focal or absent GFAP immunostaining, and shared the same DNA methylation profile. Given their morphological and epigenetic similarities, circumscribed CNS tumors with EP300/CREBBP::BCOR(L1) fusions and CNS tumors with BCOR ITD may represent variants of the same tumor type. The ependymoma-like aspect coupled with the lack of diffuse GFAP immunostaining and the presence of OLIG2 positivity are useful clues for recognizing these tumors in histopathological practice. The diagnosis should be confirmed after testing for BCOR(L1) gene fusions and BCOR ITD.https://doi.org/10.1186/s40478-024-01726-xCNS tumorBCORBCORL1CREBBPFusionEpendymoma |
| spellingShingle | Valeria Barresi Antonello Cardoni Evelina Miele Lucia Pedace Barbara Masotto Claudia Nardini Sabina Barresi Sabrina Rossi CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors Acta Neuropathologica Communications CNS tumor BCOR BCORL1 CREBBP Fusion Ependymoma |
| title | CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors |
| title_full | CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors |
| title_fullStr | CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors |
| title_full_unstemmed | CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors |
| title_short | CNS tumor with CREBBP::BCORL1 Fusion and pathogenic mutations in BCOR and CREBBP: expanding the spectrum of BCOR-altered tumors |
| title_sort | cns tumor with crebbp bcorl1 fusion and pathogenic mutations in bcor and crebbp expanding the spectrum of bcor altered tumors |
| topic | CNS tumor BCOR BCORL1 CREBBP Fusion Ependymoma |
| url | https://doi.org/10.1186/s40478-024-01726-x |
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