Li Kay Ka-Wai, Lau Kin-Mang, Ng Ho-Keung
Department of Anatomical and Cellular Pathology, The Chinese University of Hong Kong, Hong Kong.
Int J Clin Exp Pathol. 2013 Jun 15;6(7):1211-22. Print 2013.
Medulloblastoma (MB) is the most common malignant brain tumor in children. Although multimodality treatment regimens including surgery, radiotherapy and chemotherapy have greatly improved disease outcome, about one-third of MB patient remains incurable, and many long-term survivors are suffered from deleterious effects due to aggressive treatment. Understanding the signaling pathways and the genetic mechanisms contributed to MB development would be the key to develop novel therapeutic treatment strategies for improving survival and outcome of MB. In this review, we discuss the biological signaling pathways involved in MB pathogenesis. We also go through the current international consensus of four core MB subgroups namely, SHH, WNT, Group 3, and Group 4. This is adopted based on the knowledge of genomic complexity of MB as analyzed by recent high-throughput genomic technology. We talk about immunohistochemistry assays established to determine molecular subgroup affiliation. In the last part of review, we discuss how identification of molecular subgroups is going to change our routine disease diagnosis and clinical management.
髓母细胞瘤(MB)是儿童中最常见的恶性脑肿瘤。尽管包括手术、放疗和化疗在内的多模态治疗方案已极大地改善了疾病预后,但约三分之一的MB患者仍无法治愈,而且许多长期存活者因积极治疗而遭受有害影响。了解促成MB发生发展的信号通路和遗传机制将是开发新型治疗策略以提高MB患者生存率和改善预后的关键。在本综述中,我们讨论了参与MB发病机制的生物学信号通路。我们还梳理了当前关于MB四个核心亚组(即SHH、WNT、3组和4组)的国际共识。这是基于近期高通量基因组技术分析得出的MB基因组复杂性知识而采用的。我们探讨了为确定分子亚组归属而建立的免疫组织化学检测方法。在综述的最后部分,我们讨论了分子亚组的识别将如何改变我们常规的疾病诊断和临床管理。