Ramaswamy Vijay, Northcott Paul A, Taylor Michael D
Developmental and Stem Cell Biology and Division of Neurosurgery, Arthur and Sonia Labatt Brain Tumour Research Centre, The Hospital for Sick Children, Toronto, Ontario, Canada.
Cancer Genet. 2011 Nov;204(11):577-88. doi: 10.1016/j.cancergen.2011.11.001.
Rapidly evolving genomic technologies have permitted progressively detailed studies of medulloblastoma biology in recent years. These data have increased our understanding of the molecular pathogenesis of medulloblastoma, identified prognostic markers, and suggested future avenues for targeted therapy. Although current randomized trials are still stratified based largely on clinical variables, the use of molecular markers is approaching routine use in the clinic. In particular, integrated genomics has uncovered that medulloblastoma comprises four distinct molecular and clinical variants: WNT, sonic hedgehog (SHH), group 3, and group 4. Children with WNT medulloblastoma have improved survival, whereas those with group 3 medulloblastoma have a dismal prognosis. Additionally, integrated genomics has shown that adult medulloblastoma is molecularly and clinically distinct from the childhood variants. Prognostic and predictive markers identified by genomics should drive changes in stratification of treatment protocols for medulloblastoma patients on clinical trials once they can be demonstrated to be reliable, reproducible, and practical. Cases with excellent prognoses (WNT cases) should be considered for therapy de-escalation, whereas those with bleak prognoses (group 3 cases) should be prioritized for experimental therapy. In this review, we will summarize the genomic data published over the past decade and attempt to interpret its prognostic significance, relevance to the clinic, and use in upcoming clinical trials.
近年来，快速发展的基因组技术使人们能够对髓母细胞瘤生物学进行日益详细的研究。这些数据增进了我们对髓母细胞瘤分子发病机制的理解，确定了预后标志物，并为靶向治疗指明了未来方向。尽管目前的随机试验仍主要基于临床变量进行分层，但分子标志物在临床中的应用正逐渐趋于常规化。特别是，整合基因组学揭示出髓母细胞瘤包含四种不同的分子和临床亚型：WNT、音猬因子（SHH）、3组和4组。患有WNT髓母细胞瘤的儿童生存率有所提高，而患有3组髓母细胞瘤的儿童预后则很差。此外，整合基因组学表明，成人髓母细胞瘤在分子和临床上与儿童亚型不同。一旦基因组学确定的预后和预测标志物能够被证明是可靠、可重复且实用的，那么它们将推动髓母细胞瘤患者临床试验治疗方案分层的改变。预后良好的病例（WNT病例）应考虑降低治疗强度，而预后不佳的病例（3组病例）应优先接受实验性治疗。在本综述中，我们将总结过去十年发表的基因组数据，并尝试解读其预后意义、与临床的相关性以及在即将开展的临床试验中的应用。
