Journal
NEURO-ONCOLOGY
Volume 21, Issue 2, Pages 214-221Publisher
OXFORD UNIV PRESS INC
DOI: 10.1093/neuonc/noy155
Keywords
medulloblastoma; methylation analysis; stratification; WNT activated
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Funding
- Helmholtz Association Research grant
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Background. Wingless-activated medulloblastoma (WNT MB) represents a well-characterized molecular variant accounting for 10-15% of all MB and is associated with a favorable clinical outcome. Patients with localized WNT MBs could benefit from de-intensification of combined treatment, which would require an accurate diagnosis of these tumors. However, despite the presence of molecular features related with a WNT MB signature (nuclear beta-catenin immunoexpression, CTNNB1 mutation, and monosomy 6), a prompt and reliable diagnostic verification of these tumors is not yet feasible. Methods. In the current study, we analyzed 78 samples of WNT MB treated in a single institute through genomewide DNA methylation and targeted next generation sequencing to elaborate an optimal method for WNT MB molecular verification. Results. We found that DNA methylation profiling discloses significant advantages for molecular diagnostic of WNT MB. All other routine methods applied, such as beta-catenin immunohistochemistry, CTNNB1 mutation analysis, and detection of monosomy 6, failed to identify all WNT MB cases. Survival analysis revealed that application of a reduced radiotherapy protocol for WNT MB treatment had no influence on patients' survival. Only one patient died due to local relapse but recurrent tumor was pathologically and molecularly diagnosed as a secondary glioblastoma. Conclusions. DNA methylation analysis should be considered as a method of choice for further clinically relevant stratification of WNT MB and for correct diagnosis of the recurrent tumors. WNT MB patients with localized disease could benefit from treatment de-intensification.
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