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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Main Authors: Malcolm F. McDonald, Sricharan Gopakumar, Tareq A. Juratli, Ilker Y. Eyüpoglu, Ganesh Rao, Jacob J. Mandel, Ali Jalali
Format: Article
Language:English
Published: BMC 2025-01-01
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.
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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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