Abstract：
Neuroblastoma (NBL) and medulloblastoma (MB) are aggressive pediatric cancers which can benefit from therapies targeting gangliosides. Therefore, we compared the ganglioside profile of 9 MB and 14 NBL samples by thin layer chromatography and mass spectrometry. NBL had the highest expression of GD2 (median 0.54 nmol GD2/mg protein), and also expressed complex gangliosides. GD2-low samples expressed GD1a and were more differentiated. MB mainly expressed GD2 (median 0.032 nmol GD2/mg protein) or GM3. Four sonic hedgehog-activated (SHH) as well as one group 4 and one group 3 MBs were GD2-positive. Two group 3 MB samples were GD2-negative but GM3-positive. N-glycolyl neuraminic acid-containing GM3 was neither detected in NBL nor MB by mass spectrometry. Furthermore, a GD2-phenotype predicting two-gene signature (ST8SIA1 and B4GALNT1) was applied to RNA-Seq datasets, including 86 MBs and validated by qRT-PCR. The signature values were decreased in group 3 and wingless-activated (WNT) compared to SHH and group 4 MBs. These results suggest that while NBL is GD2-positive, only some MB patients can benefit from a GD2-directed therapy. The expression of genes involved in the ganglioside synthesis may allow the identification of GD2-positive MBs. Finally, the ganglioside profile may reflect the differentiation status in NBL and could help to define MB subtypes.
摘要：
神经母细胞瘤（NBL）和髓母细胞瘤（MB）是侵袭性儿科癌症，可受益于靶向神经节苷脂的治疗。因此,我们通过薄层色谱和质谱比较了9MB和14NBL样品的神经节苷脂谱。NBL的GD2表达最高（中位数为0.54nmolGD2/mg蛋白），还表达了复杂的神经节苷脂。GD2-低样品表达GD1a并且更分化。MB主要表达GD2(中位数0.032nmolGD2/mg蛋白)或GM3。四个声波刺猬激活（SHH）以及一组4和一组3MB均为GD2阳性。两组3MB样品为GD2阴性但GM3阳性。通过质谱法在NBL和MB中均未检测到含有N-羟丙基神经氨酸的GM3。此外，将预测双基因签名的GD2表型（ST8SIA1和B4GALNT1）应用于RNA-Seq数据集，包括86MB，并通过qRT-PCR进行验证。与SHH和第4组MB相比，第3组和无翼激活（WNT）组的特征值降低。这些结果表明，虽然NBL是GD2阳性，只有部分MB患者可以从GD2定向治疗中获益.参与神经节苷脂合成的基因的表达可以鉴定GD2阳性MB。最后,神经节苷脂谱可以反映NBL的分化状态,并有助于确定MB亚型.
