Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands.
Departments of Pediatric Oncology and Hematology/Pediatrics, University of Groningen, University Medical Center Groningen, Hanzeplein 1, 9700 RB Groningen, the Netherlands; Princess Máxima Center for Pediatric Oncology, Lundlaan 6, 3584 EA Utrecht, the Netherlands.
Cell Rep. 2018 Mar 20;22(12):3206-3216. doi: 10.1016/j.celrep.2018.02.089.
The brain cancer medulloblastoma consists of different transcriptional subgroups. To characterize medulloblastoma at the phosphoprotein-signaling level, we performed high-throughput peptide phosphorylation profiling on a large cohort of SHH (Sonic Hedgehog), group 3, and group 4 medulloblastomas. We identified two major protein-signaling profiles. One profile was associated with rapid death post-recurrence and resembled MYC-like signaling for which MYC lesions are sufficient but not necessary. The second profile showed enrichment for DNA damage, as well as apoptotic and neuronal signaling. Integrative analysis demonstrated that heterogeneous transcriptional input converges on these protein-signaling profiles: all SHH and a subset of group 3 patients exhibited the MYC-like protein-signaling profile; the majority of the other group 3 subset and group 4 patients displayed the DNA damage/apoptotic/neuronal signaling profile. Functional analysis of enriched pathways highlighted cell-cycle progression and protein synthesis as therapeutic targets for MYC-like medulloblastoma.
脑癌髓母细胞瘤由不同的转录亚群组成。为了在磷酸化蛋白信号水平上对髓母细胞瘤进行特征描述，我们对大量 SHH（Sonic Hedgehog）、3 组和 4 组髓母细胞瘤进行了高通量肽磷酸化谱分析。我们确定了两种主要的蛋白信号谱。一种谱与复发后的快速死亡有关，类似于 MYC 样信号，其中 MYC 病变是充分的，但不是必需的。第二种谱显示 DNA 损伤以及凋亡和神经元信号富集。综合分析表明，异质转录输入集中在这些蛋白信号谱上：所有 SHH 和一部分 3 组患者表现出 MYC 样蛋白信号谱；其他 3 组的大多数患者和 4 组患者表现出 DNA 损伤/凋亡/神经元信号谱。富集途径的功能分析强调细胞周期进展和蛋白质合成是 MYC 样髓母细胞瘤的治疗靶点。
