Expression data from neuroblastoma of TH-MYCN/KI RetM919T mice. Mus musculus

The RET gene has been identified previously as a target of activated ALK at the mRNA level in both human neuroblastoma cell lines and primary tumors as well as in murine tumors driven by mutated Alk and MYCN. Moreover, it has been shown that tumor growth of murine TH-MYCN/KI Alkmut tumors was impaired upon Ret inhibition by the vandetanib inhibitor, suggesting RET as a therapeutic target in ALK mutated neuroblastoma. To further demonstrate the crucial role of RET in ALK mutated driven neuroblastoma oncogenesis, transgenic TH-MYCN mice were bred with KI RetM919T tumors. We document an oncogenic cooperation between activated Ret and MYCN overexpression in neuroblastoma formation. We used microarrays to analyze the global programme of gene expression of MYCN/RetM919T tumors and compare these profiles with profiles of MYCN/Alkmut tumors (GSE46583). Altogether, our data show that MYCN/RetM919T tumors present with expression profiles close to MYCN/Alkmut tumors. Overall design: We selected 6 murine neuroblastoma tumors from MYCN/RetM919T mice for RNA extraction and hybridization on Affymetrix microarrays既往研究已证实，在人神经母细胞瘤细胞系、原发肿瘤，以及由突变Alk与MYCN驱动的小鼠肿瘤中，RET基因（RET）可作为激活型ALK（activated ALK）的靶基因，其表达调控发生于mRNA层面。此外，已有研究表明，使用凡德他尼（vandetanib）抑制剂抑制Ret后，携带TH-MYCN/KI Alkmut突变的小鼠肿瘤生长受到显著抑制，这提示RET可作为ALK突变型神经母细胞瘤的潜在治疗靶点。 为进一步明确RET在ALK突变驱动的神经母细胞瘤发生发展中的关键作用，本研究将转基因TH-MYCN小鼠与携带敲入（KI）RetM919T突变的小鼠进行繁育。本研究证实，激活型Ret与MYCN过表达之间存在致癌协同效应，可促进神经母细胞瘤的形成。 我们利用基因芯片（microarrays）分析了MYCN/RetM919T肿瘤的全基因表达谱，并将其与MYCN/Alkmut肿瘤的表达谱（GSE46583）进行对比。综合来看，本研究数据显示，MYCN/RetM919T肿瘤的基因表达谱与MYCN/Alkmut肿瘤高度相似。 实验整体设计：本研究从MYCN/RetM919T小鼠中选取6例神经母细胞瘤组织，进行RNA提取，并在Affymetrix基因芯片上完成杂交实验。