三维基因组拓扑学可区分髓母细胞瘤分子亚群。

IF 8.1 1区 生物学 Q1 GENETICS & HEREDITY American journal of human genetics Pub Date : 2024-10-22 DOI:10.1016/j.ajhg.2024.10.003
John J Y Lee, Michael J Johnston, Hamza Farooq, Huey-Miin Chen, Subhi Talal Younes, Raul Suarez, Melissa Zwaig, Nikoleta Juretic, William A Weiss, Jiannis Ragoussis, Nada Jabado, Michael D Taylor, Marco Gallo
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引用次数: 0

摘要

根据转录、DNA甲基化和遗传特征,已确定了四种主要的髓母细胞瘤(MB)分子亚型。然而,目前尚不清楚髓母细胞瘤亚型之间的三维基因组结构是否存在差异。为了解决这个问题,我们进行了原位 Hi-C 重建 MB 亚型的三维基因组结构。我们总共生成了 28 个手术标本的 Hi-C 和匹配的转录组数据,以及一个患者来源异种移植的 Hi-C 数据。Hi-C 图谱的平均分辨率为 6,833 bp。利用这些数据,我们发现拓扑关联结构域(TAD)的绝缘分数能有效区分 MB 分子亚群。尽管我们在特定 MB 亚型的起源谱系附近发现了一些表达基因,但亚型之间的 TAD 绝缘分数差异总体上与基因表达差异无关。因此,我们的研究支持这样一种观点,即 TAD 绝缘分数可以独立于转录差异区分 MB 亚型。
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3D genome topology distinguishes molecular subgroups of medulloblastoma.

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.

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来源期刊
CiteScore
14.70
自引率
4.10%
发文量
185
审稿时长
1 months
期刊介绍: The American Journal of Human Genetics (AJHG) is a monthly journal published by Cell Press, chosen by The American Society of Human Genetics (ASHG) as its premier publication starting from January 2008. AJHG represents Cell Press's first society-owned journal, and both ASHG and Cell Press anticipate significant synergies between AJHG content and that of other Cell Press titles.
期刊最新文献
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