The malignant transformation of an atypical angiocentric glioma, MYB-altered
Abstract According to the current World Health Organization classification of central nervous system tumors, the angiocentric glioma (AG) assigned a grade 1, characterized by recurrent MYB fusions. However, it also mentions that increased proliferative activity and other anaplastic features have bee...
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BMC
2025-07-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-025-02070-4 |
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| author | Oumaima Aboubakr Annika K. Wefers Volodia Dangouloff-Ros Alice Métais Philipp Sievers Lauren Hasty Raphaël Saffroy Gaelle Pierron Delphine Guillemot Thomas Samoyeau Nathalie Boddaert Jacques Grill Kevin Beccaria Thomas Blauwblomme Pascale Varlet Arnault Tauziède-Espariat |
| author_facet | Oumaima Aboubakr Annika K. Wefers Volodia Dangouloff-Ros Alice Métais Philipp Sievers Lauren Hasty Raphaël Saffroy Gaelle Pierron Delphine Guillemot Thomas Samoyeau Nathalie Boddaert Jacques Grill Kevin Beccaria Thomas Blauwblomme Pascale Varlet Arnault Tauziède-Espariat |
| author_sort | Oumaima Aboubakr |
| collection | DOAJ |
| description | Abstract According to the current World Health Organization classification of central nervous system tumors, the angiocentric glioma (AG) assigned a grade 1, characterized by recurrent MYB fusions. However, it also mentions that increased proliferative activity and other anaplastic features have been reported, but the clinical significance of such findings is unclear as an increased proliferative activity alone does not necessarily alter the benign behavior of AGs. Most cases with “anaplasia” were mainly described before the molecular era. Herein, we report the case of a 3-year-old female with epilepsy symptomatic of a left temporo-parietal tumor. Histopathologically, the initial tumor displayed atypical AG morphology and a proliferation index of 1%, without mitoses, or necrosis. RNA sequencing identified a MYB::QKI fusion. After several tumor recurrences, the last tumor sample showed strong evidence of a histopathological transformation into a high-grade tumor with proliferation and mitotic indexes, necrosis and microvascular proliferation. The recurrent tumor still harbored the same MYB::QKI fusion but acquired an hTERT mutation. DNA-methylation analysis classified the initial tumor as an LGG, MYB/MYBL1-altered (AG, MYB/MYBL1-altered with a calibrated score of 0.58) while the progression clustered with glioblastoma, IDH-wildtype, RTK1 (with a calibrated score of 0.33). The copy number variation both at presentation and at last recurrence (CNV) exhibited a chromosome 6 chromothripsis. The patient died from tumor progression after an overall survival of 89 months. This novel observation raises the question of whether this case represents an aggressive form of MYB/MYBL1-altered LGGs driven by an oncogenic MYB fusion, or if they are actually high-grade gliomas that coincidentally exhibit alterations near the MYB locus. Further reports are needed to confirm the existence of malignant forms of LGG, MYB/MYBL1-altered, potentially correlated with a higher grade. |
| format | Article |
| id | doaj-art-08acedc7ba4b46659a32cee2fe4e261f |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-08acedc7ba4b46659a32cee2fe4e261f2025-08-20T04:02:49ZengBMCActa Neuropathologica Communications2051-59602025-07-011311510.1186/s40478-025-02070-4The malignant transformation of an atypical angiocentric glioma, MYB-alteredOumaima Aboubakr0Annika K. Wefers1Volodia Dangouloff-Ros2Alice Métais3Philipp Sievers4Lauren Hasty5Raphaël Saffroy6Gaelle Pierron7Delphine Guillemot8Thomas Samoyeau9Nathalie Boddaert10Jacques Grill11Kevin Beccaria12Thomas Blauwblomme13Pascale Varlet14Arnault Tauziède-Espariat15Department of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalInstitute of Neuropathology, University Medical Center Hamburg-EppendorfPediatric Radiology Department, Hôpital Necker Enfants Malades, AP-HPDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalDepartment of Neuropathology, Institute of Pathology, University Hospital HeidelbergDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalDepartment of Biochemistry and Oncogenetics, Paul Brousse HospitalParis-Sciences-Lettres, INSERMU830, Institut Curie Research CenterParis-Sciences-Lettres, INSERMU830, Institut Curie Research CenterMildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-EppendorfMildred Scheel Cancer Career Center HaTriCS4, University Medical Center Hamburg-EppendorfDepartment of Child and Adolescent Oncology, Gustave RoussyDepartment of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris Cité UniversityDepartment of Pediatric Neurosurgery, Necker Enfants Malades Hospital, Paris Cité UniversityDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalDepartment of Neuropathology, GHU Paris-Psychiatrie et Neurosciences, Sainte-Anne HospitalAbstract According to the current World Health Organization classification of central nervous system tumors, the angiocentric glioma (AG) assigned a grade 1, characterized by recurrent MYB fusions. However, it also mentions that increased proliferative activity and other anaplastic features have been reported, but the clinical significance of such findings is unclear as an increased proliferative activity alone does not necessarily alter the benign behavior of AGs. Most cases with “anaplasia” were mainly described before the molecular era. Herein, we report the case of a 3-year-old female with epilepsy symptomatic of a left temporo-parietal tumor. Histopathologically, the initial tumor displayed atypical AG morphology and a proliferation index of 1%, without mitoses, or necrosis. RNA sequencing identified a MYB::QKI fusion. After several tumor recurrences, the last tumor sample showed strong evidence of a histopathological transformation into a high-grade tumor with proliferation and mitotic indexes, necrosis and microvascular proliferation. The recurrent tumor still harbored the same MYB::QKI fusion but acquired an hTERT mutation. DNA-methylation analysis classified the initial tumor as an LGG, MYB/MYBL1-altered (AG, MYB/MYBL1-altered with a calibrated score of 0.58) while the progression clustered with glioblastoma, IDH-wildtype, RTK1 (with a calibrated score of 0.33). The copy number variation both at presentation and at last recurrence (CNV) exhibited a chromosome 6 chromothripsis. The patient died from tumor progression after an overall survival of 89 months. This novel observation raises the question of whether this case represents an aggressive form of MYB/MYBL1-altered LGGs driven by an oncogenic MYB fusion, or if they are actually high-grade gliomas that coincidentally exhibit alterations near the MYB locus. Further reports are needed to confirm the existence of malignant forms of LGG, MYB/MYBL1-altered, potentially correlated with a higher grade.https://doi.org/10.1186/s40478-025-02070-4Angiocentric gliomaMYBDNA-methylation profilingAggressive |
| spellingShingle | Oumaima Aboubakr Annika K. Wefers Volodia Dangouloff-Ros Alice Métais Philipp Sievers Lauren Hasty Raphaël Saffroy Gaelle Pierron Delphine Guillemot Thomas Samoyeau Nathalie Boddaert Jacques Grill Kevin Beccaria Thomas Blauwblomme Pascale Varlet Arnault Tauziède-Espariat The malignant transformation of an atypical angiocentric glioma, MYB-altered Acta Neuropathologica Communications Angiocentric glioma MYB DNA-methylation profiling Aggressive |
| title | The malignant transformation of an atypical angiocentric glioma, MYB-altered |
| title_full | The malignant transformation of an atypical angiocentric glioma, MYB-altered |
| title_fullStr | The malignant transformation of an atypical angiocentric glioma, MYB-altered |
| title_full_unstemmed | The malignant transformation of an atypical angiocentric glioma, MYB-altered |
| title_short | The malignant transformation of an atypical angiocentric glioma, MYB-altered |
| title_sort | malignant transformation of an atypical angiocentric glioma myb altered |
| topic | Angiocentric glioma MYB DNA-methylation profiling Aggressive |
| url | https://doi.org/10.1186/s40478-025-02070-4 |
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