DNA methylation-based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification.
Date
2023-04-01ICR Author
Author
Stone, TJ
Mankad, K
Tan, AP
Jan, W
Pickles, JC
Gogou, M
Chalker, J
Slodkowska, I
Pang, E
Kristiansen, M
Madhan, GK
Forrest, L
Hughes, D
Koutroumanidou, E
Mistry, T
Ogunbiyi, O
Ahmed, SW
Cross, JH
Hubank, M
Hargrave, D
Jacques, TS
Type
Journal Article
Metadata
Show full item recordAbstract
AIMS: Glioneuronal tumours (GNTs) are poorly distinguished by their histology and lack robust diagnostic indicators. Previously, we showed that common GNTs comprise two molecularly distinct groups, correlating poorly with histology. To refine diagnosis, we constructed a methylation-based model for GNT classification, subsequently evaluating standards for molecular stratification by methylation, histology and radiology. METHODS: We comprehensively analysed methylation, radiology and histology for 83 GNT samples: a training cohort of 49, previously classified into molecularly defined groups by genomic profiles, plus a validation cohort of 34. We identified histological and radiological correlates to molecular classification and constructed a methylation-based support vector machine (SVM) model for prediction. Subsequently, we contrasted methylation, radiological and histological classifications in validation GNTs. RESULTS: By methylation clustering, all training and 23/34 validation GNTs segregated into two groups, the remaining 11 clustering alongside control cortex. Histological review identified prominent astrocytic/oligodendrocyte-like components, dysplastic neurons and a specific glioneuronal element as discriminators between groups. However, these were present in only a subset of tumours. Radiological review identified location, margin definition, enhancement and T2 FLAIR-rim sign as discriminators. When validation GNTs were classified by SVM, 22/23 classified correctly, comparing favourably against histology and radiology that resolved 17/22 and 15/21, respectively, where data were available for comparison. CONCLUSIONS: Diagnostic criteria inadequately reflect glioneuronal tumour biology, leaving a proportion unresolvable. In the largest cohort of molecularly defined glioneuronal tumours, we develop molecular, histological and radiological approaches for biologically meaningful classification and demonstrate almost all cases are resolvable, emphasising the importance of an integrated diagnostic approach.
Collections
Subject
dysembryoplastic neuroepithelial tumour
ganglioglioma
glioneuronal tumour
machine learning
molecular pathology
Humans
Brain Neoplasms
DNA Methylation
Neoplasms, Neuroepithelial
Central Nervous System Neoplasms
Radiology
Language
eng
Date accepted
2023-02-21
License start date
2023-04-01
Citation
Neuropathology and Applied Neurobiology, 2023, 49 (2), pp. e12894 -
Publisher
WILEY