WNT activated medulloblastoma (WNT MB) represent 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 ß-catenin immunoexpression, CTNNB1 mutation and monosomy 6), a prompt and reliable diagnostic verification of these tumors is not yet feasible.
In the current study, we analyzed 78 samples of WNT MB treated in a single institute through genome-wide DNA methylation and targeted next generation sequencing to elaborate an optimal method for WNT MB molecular verification.
We found that DNA-methylation profiling discloses significant advantages for molecular diagnostic of WNT MB. All other "routine" methods applied such as ß-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.
1. 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. 2. WNT MB patients with localized disease could benefit from treatment de-intensification.
Pharmacology, Toxicology and Pharmaceutical Science
1
3%
Other
3
8%
Unknown
14
35%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 26 September 2018.
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