AUTHOR=Chen Zirong , Yang Huaitao , Wang Jiajia , Long Guoxian , Xi Qingsong , Chen Tao , He Yue , Zhang Bin , Wan Feng 

TITLE=Molecular characterization of sub-frontal recurrent medulloblastomas reveals potential clinical relevance

JOURNAL=Frontiers in Neurology

VOLUME=Volume 14 - 2023

YEAR=2023

URL=https://www.frontiersin.org/journals/neurology/articles/10.3389/fneur.2023.1148848

DOI=10.3389/fneur.2023.1148848

ISSN=1664-2295

ABSTRACT=Background: Single recurrence in sub-frontal region after cerebellar medulloblastoma (MB) resection is rare and the underlying molecular characteristics have not been specifically addressed.
Methods: We summarized 2 such cases in our center. All the 5 samples of them were molecularly profiled for their genome and transcriptome signatures. 
Results: The recurrent tumors displayed genomic and transcriptomic divergence. Pathway analysis of recurrent tumors showed functional convergence in metabolism, cancer, neuroactive ligand-receptor interaction, and PI3K-AKT signaling pathways. Notably, the sub-frontal recurrent tumors had a much higher proportion (50-86%) of acquired driver mutations than reported in other recurrent locations. The acquired putative driver genes in the sub-frontal recurrent tumors functionally enriched for chromatin remodeler associated genes, such as KDM6B, SPEN, CHD4, and CHD7. Furthermore, the germline mutations of our cases showed a significantly functional convergence in focal adhesion, cell adhesion molecules, and ECM-receptor interaction. Evolutionary analysis showed that the recurrence could be derived from a single primary tumor lineage or had an intermediate phylogenetic similarity to the matched primary one.
Conclusion: Rare single sub-frontal recurrent MBs presented specific mutation signatures that might be related to the under-dose radiation. Particular attention should be paid to optimally covering the sub-frontal cribriform plate during post-operative radiotherapy targeting.