Wolfson Childhood Cancer Research Centre, Translational and Clinical Research Institute, Newcastle University Centre for Cancer, Newcastle University, Newcastle upon Tyne, UK.
Department of Applied Sciences, Northumbria University, Newcastle upon Tyne, UK.
Neuropathol Appl Neurobiol. 2023 Jun;49(3):e12903. doi: 10.1111/nan.12903.
The childhood brain tumour medulloblastoma is typically classified into multiple discrete molecular subgroups with characteristic DNA methylation and expression patterns. Several of these subgroups are used as, or proposed to be, an effective basis for treatment stratification. Here, we highlight the close connection between the findings described in a recent series of studies which, together, strongly imply a continuous association between survival outcome, the transcriptional profile of a Group3/Group4 (i.e. non-WNT/non-SHH) medulloblastoma and the specific point during early foetal cerebellar development at which initial pathogenic disruption took place. This has important implications for future efforts to model the disease by incorporating driving molecular features into their specific developmental context. This further suggests that instead of relying upon discrete DNA methylation subgroups, using expression biomarkers as the basis of a continuous risk predictor may produce a more effective risk stratification of patients with Group3/Group4 medulloblastoma.
儿童脑肿瘤髓母细胞瘤通常被分为多个离散的分子亚群，具有特征性的 DNA 甲基化和表达模式。其中有几个亚群被用作或被提议作为治疗分层的有效基础。在这里，我们强调了最近一系列研究中描述的发现之间的密切联系，这些研究共同强烈暗示了生存结果、转录谱与在早期胎儿小脑发育过程中最初发生致病破坏的特定时间之间存在连续关联。这对于未来通过将驱动分子特征纳入其特定发育背景来模拟疾病的努力具有重要意义。这进一步表明，与其依赖离散的 DNA 甲基化亚群，不如使用表达生物标志物作为连续风险预测因子的基础，可能会对 Group3/Group4 髓母细胞瘤患者进行更有效的风险分层。
