Details

Autor(en) / Beteiligte

• Stone, Thomas J.
• Mankad, Kshitij
• Tan, Ai Peng
• Jan, Wajanat
• Pickles, Jessica C.
• Gogou, Maria
• Chalker, Jane
• Slodkowska, Iwona
• Pang, Emily
• Kristiansen, Mark
• Madhan, Gaganjit K.
• Forrest, Leysa
• Hughes, Deborah
• Koutroumanidou, Eleni
• Mistry, Talisa
• Ogunbiyi, Olumide
• Ahmed, Saira W.
• Cross, J. Helen
• Hubank, Mike
• Hargrave, Darren
• Jacques, Thomas S.

Titel

DNA methylation‐based classification of glioneuronal tumours synergises with histology and radiology to refine accurate molecular stratification

Ist Teil von

• Neuropathology and applied neurobiology, 2023-04, Vol.49 (2), p.e12894-n/a

Ort / Verlag

England: Wiley Subscription Services, Inc

Erscheinungsjahr

2023

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. Histological classification of glioneuronal tumours inadequately reflects their underlying biology, and characteristic BRAF/FGFR1 variants are not always detected. As such, a proportion of cases remain unsolvable. In a large cohort of molecularly classified glioneuronal tumours, we constructed a methylation‐based classification model and identified histological and radiological features that correlate with molecular subtype. We demonstrate that combined methylation, histological and radiological classification can resolve almost all glioneuronal tumours, highlighting the importance of an integrated diagnostic approach for these tumours.