SNCA, a novel biomarker for Group 4 medulloblastomas, can inhibit tumor invasion and induce apoptosis

Summary

Medulloblastoma (MB) is the most common malignant brain tumor in childhood. It contains at least four distinct molecular subgroups. The aim of this study is to explore novel diagnostic and potential therapeutic markers within each subgroup of MB, in particular within Group 4, the largest subgroup, to facilitate diagnosis together with gene therapy. Total 106 MB samples were recruited. Tumor subtype was evaluated with the NanoString assay. Several novel tumor related genes were shown to have high subgroup sensitivity and specificity, including PDGFRA, FGFR1 and ALK in the WNT group; CCND1 in the SHH group; as well as α-synuclein (SNCA)in Group 4. Knock down and overexpression assay of SNCA demonstrated the ability of this gene on inhibiting tumor invasion and inducing apoptosis. Methylation specific PCR (MSP) and pyrosequencing analysis showed some epigenetic mechanisms rather than DNA hypermethylation may play the key role in the regulation of SNCA expression in MB tumors. In conclusion, we identify SNCA as a novel diagnostic biomarker for Group 4 medulloblastoma. Some other subgroup signature genes have also been found as candidate therapeutic targets for this tumor.

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