Genetic alterations of TP53 and OTX2 indicate increased risk of relapse in WNT medulloblastomas
In multivariable analysis, three genomic alterations were identified as independent indicators of outcome both PFS and OS, namely TP53 mutation, OTX2 gain, and monosomy 6. All relapsed patients could be identified by the first two alterations, so we suggest a risk prediction model based on these two markers.
The OTX2 Gene Induces Tumor Growth and Triggers Leptomeningeal Metastasis by Regulating the mTORC2 Signaling Pathway in Group 3 Medulloblastomas
β-catenin immunohistochemistry is routinely used to identify the WNT MB; TP53 mutation is a high-risk factor for SHH MB. MYC amplification is specific for group 3 MB and predicts poor prognoses, and CDK6 amplification is a vital feature of group 4 MB.
Results highlight the possibility that targeting H3K27me3 demethylase Jmjd3 with GSK-J4 to inhibit Shh signaling and cholesterol metabolism is a potential application to treat Shh medulloblastoma.
A group 3 medulloblastoma stem cell program is maintained by OTX2-mediated alternative splicing
study demonstrates that OTX2-mediated alternative splicing is a key determinant of cell fate decisions and highlights alternative splicing events as potential therapeutic targets to drive group 3 MB differentiation.