Journal Article

DKFZ-2018-01566

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png DNA-methylation profiling is a method of choice for molecular verification of pediatric WNT activated medulloblastomas.

Korshunov, A. (First author)DKFZ* ; Sahm, F.DKFZ* ; Zheludkova, O. ; Golanov, A. ; Stichel, D.DKFZ* ; Schrimpf, D.DKFZ* ; Ryzhova, M. ; Potapov, A. ; Habel, A.DKFZ* ; Meyer, J.DKFZ* ; Lichter, P.DKFZ* ; Jones, D.DKFZ* ; von Deimling, A.DKFZ* ; Pfister, S.DKFZ* ; Kool, M. (Last author)DKFZ*

2019
Oxford Univ. Press Oxford

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Please use a persistent id in citations: doi:10.1093/neuonc/noy155

Abstract: 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.

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Contributing Institute(s):

1. Neuropathologie (B300)
2. Molekulare Genetik (B060)
3. Pädiatrische Neuroonkologie (B062)
4. DKTK Heidelberg (L101)

Research Program(s):

1. 312 - Functional and structural genomics (POF3-312) (POF3-312)

Appears in the scientific report 2019

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Database coverage:
; Allianz-Lizenz / DFG ; Current Contents - Clinical Medicine ; IF >= 5 ; JCR ; NCBI Molecular Biology Database ; Nationallizenz ; SCOPUS ; Science Citation Index Expanded ; Thomson Reuters Master Journal List ; Web of Science Core Collection

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