Cell ( IF 45.5 ) Pub Date : 2024-07-09 , DOI: 10.1016/j.cell.2024.06.023 Michael J Johnston 1 , John J Y Lee 2 , Bo Hu 3 , Ana Nikolic 4 , Elham Hasheminasabgorji 4 , Audrey Baguette 5 , Seungil Paik 1 , Haifen Chen 6 , Sachin Kumar 7 , Carol C L Chen 6 , Selin Jessa 5 , Polina Balin 2 , Vernon Fong 2 , Melissa Zwaig 6 , Kulandaimanuvel Antony Michealraj 7 , Xun Chen 8 , Yanlin Zhang 9 , Srinidhi Varadharajan 10 , Pierre Billon 11 , Nikoleta Juretic 12 , Craig Daniels 13 , Amulya Nageswara Rao 14 , Caterina Giannini 14 , Eric M Thompson 15 , Miklos Garami 16 , Peter Hauser 16 , Timea Pocza 16 , Young Shin Ra 17 , Byung-Kyu Cho 18 , Seung-Ki Kim 18 , Kyu-Chang Wang 18 , Ji Yeoun Lee 18 , Wieslawa Grajkowska 19 , Marta Perek-Polnik 20 , Sameer Agnihotri 21 , Stephen Mack 10 , Benjamin Ellezam 22 , Alex Weil 23 , Jeremy Rich 24 , Guillaume Bourque 25 , Jennifer A Chan 26 , V Wee Yong 27 , Mathieu Lupien 28 , Jiannis Ragoussis 25 , Claudia Kleinman 29 , Jacek Majewski 6 , Mathieu Blanchette 30 , Nada Jabado 31 , Michael D Taylor 32 , Marco Gallo 33
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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.
中文翻译:
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TULIPs 装饰 PFA 室管膜瘤的三维基因组
后颅窝 A 组 (PFA) 室管膜瘤是一种在婴儿和幼儿中诊断出的致命脑癌。 PFA 线性基因组中缺乏驱动事件,导致我们在其 3D 基因组中搜索特征。在这里,我们重建了多种儿童肿瘤类型的 3D 基因组,并发现了 PFA 中的全局拓扑结构,该拓扑结构与多种人体组织中的干细胞和祖细胞高度相似。 PFA 中独有的一个显着特征是 PFA (TULIP) 中的 B 型超长程相互作用,这些区域沿着线性基因组相距很远,在 3D 核空间中以惊人的强度相互作用。 TULIP 存在于所有 PFA 样本中,并在可预测的基因组坐标处重复出现,它们的形成是由 EZHIP 的表达诱导的。 TULIP 在 PFA 样本中的普遍性表明分子原理的保守性可以用于治疗。