Medulloblastoma (MB), the most common malignant pediatric brain tumor, has high propensity to metastasize. Currently, the standard treatment for MB patients includes radiation therapy administered to the entire brain and spine for the purpose of treating or preventing against metastasis. Due to this aggressive treatment, the majority of long-term survivors will be left with permanent and debilitating neurocognitive impairment, for the 30–40% patients that fail to respond to treatment, all will relapse with terminal metastatic disease. An understanding of the underlying biology that drives MB metastasis is lacking, and is critically needed in order to develop targeted therapeutics for its prevention. To examine the metastatic biology of sonic hedgehog (SHH) MB, the human MB subgroup with the worst clinical outcome in children, we first generated a robust SmoA1-Math-GFP mouse model that reliably reproduces human SHH MB whereby metastases can be visualized under fluorescence microscopy. Lipidome alterations associated with metastasis were then investigated by applying ultra-performance liquid chromatography-mass spectrometry (UPLC-MS) under positive ionization mode to primary tumor samples collected from mice without (n = 18) and with (n = 7) metastasis. Thirty-four discriminant lipids associated with SHH MB metastasis were successfully annotated, including ceramides (Cers), sphingomyelins (SMs), triacylglycerols (TGs), diacylglycerols (DGs), phosphatidylcholines (PCs), and phosphatidic acids (PAs). This study provides deeper insights into dysregulations of lipid metabolism associated with SHH MB metastatic progression, and thus serves as a guide toward novel targeted therapies.

髓母细胞瘤（MB）是最常见的恶性儿童脑肿瘤，具有很高的转移倾向。目前，MB患者的标准治疗包括对整个大脑和脊柱进行放射治疗，以治疗或预防转移。由于这种积极的治疗，大多数长期幸存者将留下永久性的、使人衰弱的神经认知障碍，其中30-40%对治疗没有反应的患者，全部都会因晚期转移性疾病而复发。目前缺乏对驱动MB转移的基础生物学的了解，并且迫切需要了解这一点以开发预防其的靶向疗法。为了检查音刺猬 (SHH) MB（儿童临床结果最差的人类 MB 亚群）的转移生物学，我们首先生成了一个强大的 SmoA1-Math-GFP 小鼠模型，该模型可靠地复制了人类 SHH MB，从而可以在荧光下可视化转移显微镜。然后，通过在正电离模式下应用超高效液相色谱-质谱法 (UPLC-MS)，对从无转移 (n = 18) 和有转移 (n = 7) 的小鼠收集的原发性肿瘤样本，研究与转移相关的脂质 组改变 。成功注释了与 SHH MB 转移相关的 34 种判别脂质，包括神经酰胺 (Cers)、鞘磷脂 (SM)、三酰甘油 (TG)、二酰甘油 (DG)、磷脂酰胆碱 (PC) 和磷脂酸 (PA)。这项研究为与 SHH MB 转移进展相关的脂质代谢失调提供了更深入的见解，从而为新型靶向治疗提供了指导。