Abstract:
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.
摘要:
后颅窝A组(PFA)室管膜瘤是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。这里,我们从不同的儿童肿瘤类型中重建了3D基因组,并发现了PFA中的全局拓扑结构,这让人联想到各种人体组织中的干细胞和祖细胞.PFA中唯一存在的一个显着特征是PFA中的B型超远距离相互作用(TULIPs),沿着线性基因组间隔很远的区域,这些区域在3D核空间中以惊人的强度相互作用。TULIP发生在所有PFA样品中,并在可预测的基因组坐标处复发,它们的形成是由EZHIP的表达诱导的。TULIP在PFA样品中的普遍性表明可以在治疗上利用的分子原理的保守性。