Department of Human Anatomy and Cell Science, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Department of Obstetrics, Gynecology and Reproductive Sciences, University of Manitoba, Winnipeg, MB R3T 2N2, Canada.
Int J Mol Sci. 2024 Jul 9;25(14):7506. doi: 10.3390/ijms25147506.
Survival of Medulloblastoma (MB) depends on various factors, including the gene expression profiles of MB tumor tissues. In this study, we identified 967 MB survival-related genes (SRGs) using a gene expression dataset and the Cox proportional hazards regression model. Notably, the SRGs were over-represented on chromosomes 6 and 17, known for the abnormalities monosomy 6 and isochromosome 17 in MB. The most significant SRG was (high mobility group AT-hook 1) on chromosome 6, which is a known oncogene and a histone H1 competitor. High expression of was associated with worse survival, primarily in the Group 3γ subtype. The high expression of was unrelated to any known somatic copy number alteration. Most SRGs on chromosome 17p were associated with low expression in Group 4β, the MB subtype, with 93% deletion of 17p and 98% copy gain of 17q. GO enrichment analysis showed that both chromosomes 6 and 17 included SRGs related to telomere maintenance and provided a rationale for testing telomerase inhibitors in Group 3 MBs. We conclude that , along with other SRGs on chromosomes 6 and 17, warrant further investigation as potential therapeutic targets in selected subgroups or subtypes of MB.
成神经管细胞瘤(MB)的生存取决于多种因素,包括 MB 肿瘤组织的基因表达谱。在这项研究中,我们使用基因表达数据集和 Cox 比例风险回归模型确定了 967 个与 MB 生存相关的基因(SRG)。值得注意的是,SRGs 在染色体 6 和 17 上过度表达,这两个染色体以 MB 中的单体 6 和等臂染色体 17 异常为特征。最显著的 SRG 是染色体 6 上的 (高迁移率族 AT 钩 1),它是一种已知的癌基因和组蛋白 H1 竞争者。 的高表达与生存较差相关,主要是在 3γ 亚型中。 的高表达与任何已知的体细胞拷贝数改变无关。染色体 17p 上的大多数 SRGs 与 MB 亚型 4β 中的低表达相关,其中 17p 缺失 93%,17q 拷贝数增加 98%。GO 富集分析表明,染色体 6 和 17 都包含与端粒维持相关的 SRGs,这为在 3 型 MB 中测试端粒酶抑制剂提供了依据。我们的结论是, 与染色体 6 和 17 上的其他 SRGs 一起,值得进一步研究,作为特定亚组或 MB 亚型的潜在治疗靶点。