DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases

Introduction: Patients with suspected neuro-oncological disease on radiographic images and no histopathological evidence of a tumor on the surgically retrieved tissue, pose a great challenge for clinicians and neuropathologists. Meanwhile, genome-wide DNA methylation-based molecular profiling has be...

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Main Authors: Christian Uhl, Naseem Ayoub, Katharina Faust, Peter Vajkoczy, Leonille Schweizer, Josefine Radke, Felix Ehret, David Capper, Julia Sophie Onken
Format: Article
Language:English
Published: Elsevier 2025-01-01
Series:Brain and Spine
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Online Access:http://www.sciencedirect.com/science/article/pii/S277252942500075X
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author Christian Uhl
Naseem Ayoub
Katharina Faust
Peter Vajkoczy
Leonille Schweizer
Josefine Radke
Felix Ehret
David Capper
Julia Sophie Onken
author_facet Christian Uhl
Naseem Ayoub
Katharina Faust
Peter Vajkoczy
Leonille Schweizer
Josefine Radke
Felix Ehret
David Capper
Julia Sophie Onken
author_sort Christian Uhl
collection DOAJ
description Introduction: Patients with suspected neuro-oncological disease on radiographic images and no histopathological evidence of a tumor on the surgically retrieved tissue, pose a great challenge for clinicians and neuropathologists. Meanwhile, genome-wide DNA methylation-based molecular profiling has been established to allow robust brain tumor classification. Research question: Does DNA methylation-based molecular profiling make a relevant contribution to the diagnosis and resolution of these non-specific neuro-oncological cases. Materials and methods: We screened all neurosurgical cases at our institution between 2009 and 2021 with suspected neuro-oncological diseases on MRI but negative or unspecific histopathological diagnosis. We differentiated two groups: cases with cell-enriched, reactive tissue (with or without suspected single tumor cells), insufficient to classify the lesion according to WHO 2021 diagnostic criteria for CNS tumors (group 1) and cases that were not cell-enriched, without reactive changes and no suspected tumor cells (group 2). The primary endpoint of the study was to assess the feasibility of establishing a molecular diagnosis in accordance with the WHO 2021 diagnostic criteria for CNS tumors. Results: 23 cases with unspecified histopathological diagnosis were identified, 16 cases were assigned to group 1, seven cases to group 2. DNA-methylation-based profiling and copy number variations enabled a tumor diagnosis in nine (56.3 %) cases in group 1 and three (42.9 %) cases in group 2, adding up to 12 tumors (52.2 %). Five cases were identified as physiological cortex. Discussion and conclusion: Our findings underscore the potential of integrating DNA methylation-based profiling into diagnostic workflows, contributing to an accurate diagnosis in challenging cases.
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spelling doaj-art-7420e96f3dfe4ca4b88eeaed4a3b64f32025-08-20T02:29:42ZengElsevierBrain and Spine2772-52942025-01-01510425610.1016/j.bas.2025.104256DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological casesChristian Uhl0Naseem Ayoub1Katharina Faust2Peter Vajkoczy3Leonille Schweizer4Josefine Radke5Felix Ehret6David Capper7Julia Sophie Onken8Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Berlin, GermanyUniklinik Düsseldorf, Department of Neurosurgery, Dusseldorf, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Berlin, GermanyInstitute of Neurology (Edinger Institute), University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany; German Cancer Consortium (DKTK), Partner Site Frankfurt/Mainz, German Cancer Research Center (DKFZ), Heidelberg, Germany; Frankfurt Cancer Institute (FCI), Frankfurt am Main, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité – Universitätsmedizin Berlin, Germany; University Medicine Greifswald, Institute of Pathology, Greifswald, Germany; Berlin Institute of Health, at Charité-Universitätsmedizin Berlin, Berlin, GermanyGerman Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité – Universitätsmedizin Berlin, Germany; Charité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Radiation Oncology, Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neuropathology, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité – Universitätsmedizin Berlin, GermanyCharité – Universitätsmedizin Berlin, Corporate Member of Freie Universität Berlin and Humboldt-Universität zu Berlin, Department of Neurosurgery, Berlin, Germany; German Cancer Consortium (DKTK), partner site Berlin, a partnership between DKFZ and Charité – Universitätsmedizin Berlin, Germany; Corresponding author. Charité – Universitätsmedizin Berlin, Department of Neurosurgery, Charitéplatz 1, 10117, Berlin, Germany.Introduction: Patients with suspected neuro-oncological disease on radiographic images and no histopathological evidence of a tumor on the surgically retrieved tissue, pose a great challenge for clinicians and neuropathologists. Meanwhile, genome-wide DNA methylation-based molecular profiling has been established to allow robust brain tumor classification. Research question: Does DNA methylation-based molecular profiling make a relevant contribution to the diagnosis and resolution of these non-specific neuro-oncological cases. Materials and methods: We screened all neurosurgical cases at our institution between 2009 and 2021 with suspected neuro-oncological diseases on MRI but negative or unspecific histopathological diagnosis. We differentiated two groups: cases with cell-enriched, reactive tissue (with or without suspected single tumor cells), insufficient to classify the lesion according to WHO 2021 diagnostic criteria for CNS tumors (group 1) and cases that were not cell-enriched, without reactive changes and no suspected tumor cells (group 2). The primary endpoint of the study was to assess the feasibility of establishing a molecular diagnosis in accordance with the WHO 2021 diagnostic criteria for CNS tumors. Results: 23 cases with unspecified histopathological diagnosis were identified, 16 cases were assigned to group 1, seven cases to group 2. DNA-methylation-based profiling and copy number variations enabled a tumor diagnosis in nine (56.3 %) cases in group 1 and three (42.9 %) cases in group 2, adding up to 12 tumors (52.2 %). Five cases were identified as physiological cortex. Discussion and conclusion: Our findings underscore the potential of integrating DNA methylation-based profiling into diagnostic workflows, contributing to an accurate diagnosis in challenging cases.http://www.sciencedirect.com/science/article/pii/S277252942500075XNeuro-oncologyNeurosurgeryGenome-wide DNA methylation profilingCopy number variationGliomaHistopathologically unspecifiable tissue
spellingShingle Christian Uhl
Naseem Ayoub
Katharina Faust
Peter Vajkoczy
Leonille Schweizer
Josefine Radke
Felix Ehret
David Capper
Julia Sophie Onken
DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases
Brain and Spine
Neuro-oncology
Neurosurgery
Genome-wide DNA methylation profiling
Copy number variation
Glioma
Histopathologically unspecifiable tissue
title DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases
title_full DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases
title_fullStr DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases
title_full_unstemmed DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases
title_short DNA methylation-based profiling is an effective asset for identification of tumors in suspected, yet immunohistochemically, unspecified neuro-oncological cases
title_sort dna methylation based profiling is an effective asset for identification of tumors in suspected yet immunohistochemically unspecified neuro oncological cases
topic Neuro-oncology
Neurosurgery
Genome-wide DNA methylation profiling
Copy number variation
Glioma
Histopathologically unspecifiable tissue
url http://www.sciencedirect.com/science/article/pii/S277252942500075X
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