Unclassifiable CNS tumors in DNA methylation-based classification : clinical challenges and prognostic impact
© 2024. The Author(s)..
DNA methylation analysis has become a powerful tool in neuropathology. Although DNA methylation-based classification usually shows high accuracy, certain samples cannot be classified and remain clinically challenging. We aimed to gain insight into these cases from a clinical perspective. To address, central nervous system (CNS) tumors were subjected to DNA methylation profiling and classified according to their calibrated score using the DKFZ brain tumor classifier (V11.4) as "≥ 0.84" (score ≥ 0.84), "0.3-0.84" (score 0.3-0.84), or "< 0.3" (score < 0.3). Histopathology, patient characteristics, DNA input amount, and tumor purity were correlated. Clinical outcome parameters were time to treatment decision, progression-free, and overall survival. In 1481 patients, the classifier identified 69 (4.6%) tumors with an unreliable score as "< 0.3". Younger age (P < 0.01) and lower tumor purity (P < 0.01) compromised accurate classification. A clinical impact was demonstrated as unclassifiable cases ("< 0.3") had a longer time to treatment decision (P < 0.0001). In a subset of glioblastomas, these cases experienced an increased time to adjuvant treatment start (P < 0.001) and unfavorable survival (P < 0.025). Although DNA methylation profiling adds an important contribution to CNS tumor diagnostics, clinicians should be aware of a potentially longer time to treatment initiation, especially in malignant brain tumors.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2024 |
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| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:12 |
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| Enthalten in: |
Acta neuropathologica communications - 12(2024), 1 vom: 16. Jan., Seite 9 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Drexler, Richard [VerfasserIn] |
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| Links: |
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| Themen: |
Brain tumor classification |
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| Anmerkungen: |
Date Completed 18.01.2024 Date Revised 19.01.2024 published: Electronic Citation Status MEDLINE |
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| doi: |
10.1186/s40478-024-01728-9 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM367197138 |
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| 520 | |a DNA methylation analysis has become a powerful tool in neuropathology. Although DNA methylation-based classification usually shows high accuracy, certain samples cannot be classified and remain clinically challenging. We aimed to gain insight into these cases from a clinical perspective. To address, central nervous system (CNS) tumors were subjected to DNA methylation profiling and classified according to their calibrated score using the DKFZ brain tumor classifier (V11.4) as "≥ 0.84" (score ≥ 0.84), "0.3-0.84" (score 0.3-0.84), or "< 0.3" (score < 0.3). Histopathology, patient characteristics, DNA input amount, and tumor purity were correlated. Clinical outcome parameters were time to treatment decision, progression-free, and overall survival. In 1481 patients, the classifier identified 69 (4.6%) tumors with an unreliable score as "< 0.3". Younger age (P < 0.01) and lower tumor purity (P < 0.01) compromised accurate classification. A clinical impact was demonstrated as unclassifiable cases ("< 0.3") had a longer time to treatment decision (P < 0.0001). In a subset of glioblastomas, these cases experienced an increased time to adjuvant treatment start (P < 0.001) and unfavorable survival (P < 0.025). Although DNA methylation profiling adds an important contribution to CNS tumor diagnostics, clinicians should be aware of a potentially longer time to treatment initiation, especially in malignant brain tumors | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 4 | |a CNS tumor | |
| 650 | 4 | |a Methylation | |
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| 700 | 1 | |a Sauvigny, Jennifer |e verfasserin |4 aut | |
| 700 | 1 | |a Ricklefs, Franz L |e verfasserin |4 aut | |
| 700 | 1 | |a Eckhardt, Alicia |e verfasserin |4 aut | |
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| 700 | 1 | |a Lamszus, Katrin |e verfasserin |4 aut | |
| 700 | 1 | |a Westphal, Manfred |e verfasserin |4 aut | |
| 700 | 1 | |a Schüller, Ulrich |e verfasserin |4 aut | |
| 700 | 1 | |a Mohme, Malte |e verfasserin |4 aut | |
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