WNT Medulloblastoma: More than just β-Catenin Mutations – Rare Genetic Features in the Focus

T Goschzik; E Dörner; A zur Mühlen; T Pietsch

doi:10.1055/s-0039-1687126

Klinische Pädiatrie, Table of Contents

Klin Padiatr 2019; 231(03): 158
DOI: 10.1055/s-0039-1687126

Abstracts

Georg Thieme Verlag KG Stuttgart · New York

WNT Medulloblastoma: More than just β-Catenin Mutations – Rare Genetic Features in the Focus

Authors

T Goschzik

¹Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany
E Dörner

¹Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany
A zur Mühlen

¹Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany
T Pietsch

¹Institute of Neuropathology, University of Bonn Medical Center, Bonn, Germany

Abstract

Full Text

WNT-activated medulloblastomas (MB) account for ˜10% of all MB cases and represent low-risk tumours with overall survival rates > 90% in children. Nearly all WNT MB show classic histology and widespread nuclear accumulation of β-catenin related to CTNNB1 mutations (> 90%). In CTNNB1 wildtype tumours APC mutations have been described. Additional TP53 mutations (in ˜15% of cases) have been published as not correlated to worse outcome. Apart from monosomy 6 (˜85%), WNT tumours have relatively stable genomes. In a cohort of 152 WNT MB we identified APC mutations in 9 of 14 CTNNB1-wildtype tumours with chr. 5q aberrations in 8 of these 9 cases by molecular inversion probe array, NGS, and Sanger sequencing. In the other 5 wildtype cases one AXIN2 mutation and one homozygous loss of FBXW7 led to WNT activation, while in 3 cases no causative mutations were found. In 9 relapsed WNT tumours we identified 4 TP53 mutations; in one case a de novo mutation was found in the relapse. TP53 mutations were associated with chr. 17 p loss and p53 nuclear positivity. The clinical relevance of such alternative/additional mutational events has to be analyzed in homogenously treated patient cohorts.