Circumvention of the p53 checkpoint in neuroblastoma (NB) might arise from increased expression of its main negative regulator MDM2. The SNP309, a T-to-G substitution in the MDM2 promoter, was associated with higher levels of MDM2 mRNA and protein, with consequent attenuation of the p53 pathway. The association between MDM2 SNP309 and disease progression and survival was evaluated in a cohort of 142 children with stage 4 NB. The SNP309 GG patients had a worse overall survival and a worse survival after relapse than the TT ones, whereas the heterozygotes showed an intermediate behaviour (p=0.043 and p=0.049, respectively, log-rank test for trend). No evident association between SNP309 and event free survival was found. The lack of association between SNP309 and MYCN status indicates that MDM2 SNP309 may be a new independent prognostic factor for stage 4 NB.

译文

:在神经母细胞瘤(NB)中p53检查点的规避可能是由于其主要的负调节因子MDM2的表达增加所致。 SNP309是MDM2启动子中的T-to-G取代,与更高水平的MDM2 mRNA和蛋白质有关,因此减弱了p53途径。在142名4级NB儿童中评估了MDM2 SNP309与疾病进展和生存之间的关联。 SNP309 GG患者的总体生存率和复发后生存率均比TT差,而杂合子表现出中等的行为(趋势的对数检验分别为p = 0.043和p = 0.049)。没有发现SNP309与无事件生存之间的明显关联。 SNP309和MYCN状态之间缺乏关联性表明MDM2 SNP309可能是4期NB的新的独立预后因素。

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