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Multi-omics analysis of intertumoral heterogeneity within medulloblastoma uncharted-pathway subtypes
Brain Tumor Pathology ( IF 2.7 ) Pub Date : 2021-06-28 , DOI: 10.1007/s10014-021-00400-7
Zhicen Li 1 , Yifan Wei 2 , Yanqiu Shao 2 , Lei Tang 2 , Jian Gong 1
Affiliation  

Medulloblastoma is a common pediatric malignant brain tumor. There were four consensus molecular subgroups (WNT, SHH, Group3 and Group4). Group 3 and Group 4 tumors exhibited a great degree of transcriptional overlap, and were neither derived from exact pathway aberration. We investigated transcriptional and chromatin accessibility of medulloblastoma by multi-omics single-cell analysis. Our work identified inter- and intra-tumoral heterogeneity within the Group 3, Group 4 and Group 3/4 intermediate subgroups. Unsupervised cluster of each tumor identified 9 cell clusters with transcriptional profiles and 6 cell clusters with chromatin accessibility profiles. OTX2 had the highest activity and expression level across the clusters in a special cluster based on open chromatin single-cell profilings. We identified multiple genes as a significant targeted gene within the OTX2 target genes, which made sense in prognosis. We analyzed the copy-number-variations which presented with expected subgroup distribution from transcriptional and chromatin accessibility profiles. Collectively, these data provide novel insights into Group 3 and Group 4 medulloblastoma and provide a potential therapeutic target.



中文翻译:

髓母细胞瘤未知通路亚型内肿瘤间异质性的多组学分析

髓母细胞瘤是一种常见的小儿恶性脑肿瘤。有四个共有分子亚组(WNT、SHH、Group3 和 Group4)。第 3 组和第 4 组肿瘤表现出很大程度的转录重叠,并且都不是源自确切的途径异常。我们通过多组学单细胞分析研究了成神经管细胞瘤的转录和染色质可及性。我们的工作确定了第 3 组、第 4 组和第 3/4 组中间亚组内的肿瘤间和肿瘤内异质性。每个肿瘤的无监督簇确定了 9 个具有转录特征的细胞簇和 6 个具有染色质可及性特征的细胞簇。OTX2 在基于开放染色质单细胞分析的特殊簇中的簇中具有最高的活性和表达水平。我们确定了多个基因作为 OTX2 靶基因中的重要靶基因,这在预后中是有意义的。我们分析了从转录和染色质可及性分布中呈现出预期亚组分布的拷贝数变异。总的来说,这些数据为第 3 组和第 4 组髓母细胞瘤提供了新的见解,并提供了潜在的治疗靶点。

更新日期:2021-06-28
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