TULIPs 装点 PFA 室管膜瘤的三维基因组。
TULIPs decorate the three-dimensional genome of PFA ependymoma.
机构信息
Arnie Charbonneau Cancer Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada; Alberta Children's Hospital Research Institute, Cumming School of Medicine, University of Calgary, Calgary, AB T2N 4N1, Canada.
The Arthur and Sonia Labatt Brain Tumor Research Center, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Developmental & Stem Cell Biology Program, The Hospital for Sick Children, Toronto, ON M5G 0A4, Canada; Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON M5G 1L7, Canada.
出版信息
Cell. 2024 Sep 5;187(18):4926-4945.e22. doi: 10.1016/j.cell.2024.06.023. Epub 2024 Jul 9.
Posterior fossa group A (PFA) ependymoma is a lethal brain cancer diagnosed in infants and young children. The lack of driver events in the PFA linear genome led us to search its 3D genome for characteristic features. Here, we reconstructed 3D genomes from diverse childhood tumor types and uncovered a global topology in PFA that is highly reminiscent of stem and progenitor cells in a variety of human tissues. A remarkable feature exclusively present in PFA are type B ultra long-range interactions in PFAs (TULIPs), regions separated by great distances along the linear genome that interact with each other in the 3D nuclear space with surprising strength. TULIPs occur in all PFA samples and recur at predictable genomic coordinates, and their formation is induced by expression of EZHIP. The universality of TULIPs across PFA samples suggests a conservation of molecular principles that could be exploited therapeutically.
后颅窝 A 组（PFA）室管膜瘤是一种致命的脑癌，发生于婴儿和幼儿。PFA 线性基因组中缺乏驱动事件，这促使我们在其 3D 基因组中寻找特征。在这里，我们从各种儿童肿瘤类型中重建了 3D 基因组，并揭示了 PFA 中的一种全局拓扑结构，该结构高度类似于各种人体组织中的干细胞和祖细胞。在 PFA 中，一个显著的特征是 B 型超长距离相互作用（TULIPs），它们沿着线性基因组在很大的距离上分离，但在 3D 核空间中以惊人的强度相互作用。TULIPs 存在于所有 PFA 样本中，并且在可预测的基因组坐标处重现，其形成是由 EZHIP 表达诱导的。TULIPs 在所有 PFA 样本中的普遍性表明，分子原理可能具有保守性，可以被治疗性地利用。
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