Investigation of a Novel Cancer Stem Cell Population in Ependymoma.

项目总结 脑瘤已成为儿童癌症相关死亡的主要原因。室管膜瘤(EPN) 与髓母细胞瘤不同的是，这些死亡中有很大一部分原因是没有有效的化疗 已经被确认了。与成人不同，大多数儿科室管膜瘤发生在后颅窝。而当 积极的手术和放疗改善了最初的效果，但即使在完全切除和放疗的情况下也是如此。 后颅窝室管膜瘤的10年进展存活率非常低，只有大约三分之一 这些孩子没有复发。所有复发的室管膜瘤儿童将再次复发，所有人都将死亡， 通常在多次复发后，进行破坏性的重复手术和放射治疗。迫切需要 更好地了解这些肿瘤的生物学特性，以了解高复发率，并经常延迟复发。散装 对儿童室管膜瘤样本的检查可以将室管膜瘤分型 确定了具有早期复发风险的亚群，但对治疗或长期结果没有影响。 鉴于复发的时间较晚，最常见于接受过完整手术的儿童 辐射后，我们假设复发发生在相对较少数量的耐药癌症干细胞 在诊断时出现。应用单细胞RNA序列检测后颅窝室管膜瘤强化的初步数据 这一假设，并在4个不同的亚群中确定了一个假定的癌症干细胞亚群。 这项拨款严格地探索了我们是否确实在儿童时期发现了癌症干细胞群体。 室管膜瘤。我们的研究旨在充分描述已确定的不同的室管膜瘤亚群。 在单细胞RNA序列中。除了手术和治疗外，还有可能在诊断时瞄准干细胞群体 对于死亡率相当高的儿童脑瘤，放射治疗可能会改善其预后。

PROJECT SUMMARY Brain tumors have become the leading cause of cancer-related death in children. Ependymoma (EPN) accounts for a substantial number of these deaths, and unlike in medulloblastoma, no effective chemotherapy has been identified. Most pediatric ependymomas, unlike in adults, occur in the posterior fossa. While aggressive surgery and radiation improve the initial results but even in completely resected and radiated posterior fossa ependymoma the 10-year progression survival is very poor with only approximately one third of these children being without relapse. All relapsed children with ependymoma will relapse again and all will die, often after multiple relapses with damaging repeated surgeries and radiation. There is a desperate need to understand the biology of these tumors better to understand the high, and often delayed, relapses. Bulk examination of childhood ependymoma samples has allowed classification within ependymoma which has had identified subpopulations with early relapse risk but has had no impact on therapy or long-term outcomes. Given that relapses are late, seen most frequently in children who have had complete surgeries and are radiated, we hypothesized that relapses occur from a relatively small number of resistant cancer stem cells present at diagnosis. Preliminary data using single cell RNA seq on posterior fossa ependymoma strengthens this hypothesis and identifies a putative cancer stem cell subpopulation amongst 4 distinct subpopulations. This grant rigorously explores whether we have indeed identified a cancer stem population in childhood ependymoma. Our research intends to fully characterizes the distinct ependymoma subpopulations identified in single cell RNA seq. Potentially targeting a stem cell population at diagnosis in addition to surgery and radiation may improved outcomes for a pediatric brain tumor that has substantial mortality.