Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated
Abstract Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontigu...
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| Format: | Article |
| Language: | English |
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BMC
2025-01-01
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| Series: | Acta Neuropathologica Communications |
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| Online Access: | https://doi.org/10.1186/s40478-024-01900-1 |
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| author | Malcolm F. McDonald Sricharan Gopakumar Tareq A. Juratli Ilker Y. Eyüpoglu Ganesh Rao Jacob J. Mandel Ali Jalali |
| author_facet | Malcolm F. McDonald Sricharan Gopakumar Tareq A. Juratli Ilker Y. Eyüpoglu Ganesh Rao Jacob J. Mandel Ali Jalali |
| author_sort | Malcolm F. McDonald |
| collection | DOAJ |
| description | Abstract Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences and initial tumors, supporting a common origin. Discontiguous recurrences were more likely to be hypermutated compared to contiguous recurrences (p = 0.038). Analysis of 2 glioblastoma cases with discontiguous recurrence at a collaborating institution also exhibited hypermutation. In conclusion, discontiguous glioblastoma recurrences share a common origin with the initial tumor and are more likely to be hypermutated than contiguous recurrences. |
| format | Article |
| id | doaj-art-9771a7a8d58d446cbbcf0f579b63c1d4 |
| institution | Kabale University |
| issn | 2051-5960 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Acta Neuropathologica Communications |
| spelling | doaj-art-9771a7a8d58d446cbbcf0f579b63c1d42025-01-19T12:42:46ZengBMCActa Neuropathologica Communications2051-59602025-01-011311910.1186/s40478-024-01900-1Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutatedMalcolm F. McDonald0Sricharan Gopakumar1Tareq A. Juratli2Ilker Y. Eyüpoglu3Ganesh Rao4Jacob J. Mandel5Ali Jalali6Department of Neurosurgery, Baylor College of MedicineDepartment of Neurosurgery, Baylor College of MedicineDepartment of Neurosurgery, Faculty of Medicine, Carl Gustav Carus University Hospital, Technische Universität DresdenDepartment of Neurosurgery, Faculty of Medicine, Carl Gustav Carus University Hospital, Technische Universität DresdenDepartment of Neurosurgery, Baylor College of MedicineDepartment of Neurology, Baylor College of MedicineDepartment of Neurosurgery, Baylor College of MedicineAbstract Glioblastoma is the deadliest primary brain tumor, largely due to inevitable recurrence of the disease after treatment. While most recurrences are local, patients rarely present with a new discontiguous focus of glioblastoma. Little is currently known about the genetic profile of discontiguous recurrences. In our institutional database, we identified 22 patients with targeted exome sequencing of pairs of initial and recurrent IDH-wildtype glioblastoma. Recurrences were classified as contiguous or discontiguous based on the presence or absence of T2 FLAIR signal connection to the initial site of disease on MRI. Exome analysis revealed shared driver and passenger mutations between discontiguous recurrences and initial tumors, supporting a common origin. Discontiguous recurrences were more likely to be hypermutated compared to contiguous recurrences (p = 0.038). Analysis of 2 glioblastoma cases with discontiguous recurrence at a collaborating institution also exhibited hypermutation. In conclusion, discontiguous glioblastoma recurrences share a common origin with the initial tumor and are more likely to be hypermutated than contiguous recurrences.https://doi.org/10.1186/s40478-024-01900-1IDH WT gliomaGlioblastoma recurrenceMulticentricDiscontiguousHypermutation |
| spellingShingle | Malcolm F. McDonald Sricharan Gopakumar Tareq A. Juratli Ilker Y. Eyüpoglu Ganesh Rao Jacob J. Mandel Ali Jalali Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated Acta Neuropathologica Communications IDH WT glioma Glioblastoma recurrence Multicentric Discontiguous Hypermutation |
| title | Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated |
| title_full | Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated |
| title_fullStr | Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated |
| title_full_unstemmed | Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated |
| title_short | Discontiguous recurrences of IDH-wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated |
| title_sort | discontiguous recurrences of idh wildtype glioblastoma share a common origin with the initial tumor and are frequently hypermutated |
| topic | IDH WT glioma Glioblastoma recurrence Multicentric Discontiguous Hypermutation |
| url | https://doi.org/10.1186/s40478-024-01900-1 |
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