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Abstract：
Medulloblastoma is the most common pediatric malignant brain tumor. Advances in molecular profiling have uncovered significant heterogeneity among medulloblastomas and led to the identification of four distinct subgroups (wingless [WNT], sonic hedgehog [SHH], group 3, and group 4) that represent distinct disease entities in both underlying biology and clinical characteristics. The rapidly expanding repertoire of tools to study developmental and cancer biology is providing a wealth of knowledge about these embryonal tumors and is continuously refining the understanding of this complex cancer. In this review, the history of discovery in medulloblastoma is discussed, setting a foundation to outline the current state of understanding of the molecular underpinnings of this disease, with a focus on genomic events that define the aforementioned subgroups and evolving areas of focus, such as the cell of origin of medulloblastoma and medulloblastoma subtypes. With these recent discoveries in mind, the current state of medulloblastoma treatment and clinical trials is reviewed, including a novel risk stratification system that accounts for the molecular biomarkers of patients with a high risk for refractory disease. Lastly, critical areas of focus for future basic science and clinical research on this disease are discussed, such as the complexities of medulloblastoma metastases and recurrence as well as the priorities and strategies to implement in future clinical trials.
摘要：
髓母细胞瘤是最常见的小儿恶性脑肿瘤。分子谱分析的进展揭示了髓母细胞瘤之间的显着异质性，并导致四个不同的亚组的鉴定（无翼[WNT]，索尼克刺猬[SHH]，第3组和第4组）代表了潜在生物学和临床特征的不同疾病实体。研究发育和癌症生物学的快速扩展的工具库提供了有关这些胚胎肿瘤的丰富知识，并不断加深对这种复杂癌症的理解。在这次审查中,讨论了髓母细胞瘤的发现历史，为概述目前对这种疾病的分子基础的理解奠定了基础，关注定义上述亚组和不断发展的关注领域的基因组事件，如髓母细胞瘤的细胞起源和髓母细胞瘤亚型。考虑到这些最近的发现，综述了髓母细胞瘤治疗和临床试验的现状，包括一种新的风险分层系统，该系统可解释难治性疾病高风险患者的分子生物标志物。最后,讨论了该疾病未来基础科学和临床研究的重点领域，如髓母细胞瘤转移和复发的复杂性，以及在未来临床试验中实施的优先事项和策略。
