Four main medulloblastoma (MB) molecular subtypes have been identified based on transcriptional, DNA methylation, and genetic profiles. However, it is currently not known whether 3D genome architecture differs between MB subtypes. To address this question, we performed in situ Hi-C to reconstruct the 3D genome architecture of MB subtypes. In total, we generated Hi-C and matching transcriptome data for 28 surgical specimens and Hi-C data for one patient-derived xenograft. The average resolution of the Hi-C maps was 6,833 bp. Using these data, we found that insulation scores of topologically associating domains (TADs) were effective at distinguishing MB molecular subgroups. TAD insulation score differences between subtypes were globally not associated with differential gene expression, although we identified few exceptions near genes expressed in the lineages of origin of specific MB subtypes. Our study therefore supports the notion that TAD insulation scores can distinguish MB subtypes independently of their transcriptional differences.

中文翻译：

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3D 基因组拓扑结构区分髓母细胞瘤的分子亚群


已根据转录、DNA 甲基化和遗传谱确定了四种主要的髓母细胞瘤 （MB） 分子亚型。然而，目前尚不清楚 MB 亚型之间的 3D 基因组结构是否不同。为了解决这个问题，我们进行了原位 Hi-C 重建 MB 亚型的 3D 基因组结构。我们总共为 28 个手术标本生成了 Hi-C 和匹配的转录组数据，并为 1 个患者来源的异种移植物生成了 Hi-C 数据。Hi-C 图的平均分辨率为 6,833 bp。利用这些数据，我们发现拓扑关联结构域 （TAD） 的绝缘评分可有效区分 MB 分子亚群。亚型之间的 TAD 绝缘评分差异与差异基因表达无关，尽管我们在特定 MB 亚型的起源谱系中表达的基因附近发现了一些例外。因此，我们的研究支持 TAD 绝缘评分可以独立于转录差异区分 MB 亚型的观点。