肾母细胞瘤中IGF-2外显子9甲基化状态与IGF-2表达关系的初步研究

The Relationship between Abnormal Methylation of IGF-2 Exon 9 and Wilms Tumor

目的:探讨胰岛素样生长因子(IGF-2)外显子9CpG岛甲基化状态与IGF-2基因表达的关系,以进一步探究肾母细胞瘤发生机制。方法:应用甲基化敏感性限制性内切酶PCR和等位基因特异性IGF-2基因表达分析,检测42例肾母细胞瘤及相应正常组织的IGF-2外显子9甲基化状态及IGF-2基因表达。结果:肾母细胞瘤IGF-2外显子9甲基化率为16.6%,瘤旁组织为95.2%,两者差异有统计学意义(P<0.01),其中以胚基细胞为主型肾母细胞瘤IGF-2外显子9去甲基化率高于上皮细胞优势型和间质细胞优势型的肾母细胞瘤(P<0.01),在低分化间变型肾母细胞瘤中IGF-2外显子9去甲基化率显著高于高分化无间变型肾母细胞瘤(P<0.01)。外显子9去甲基化组织中IGF-2双等位基因表达率显著高于甲基化的组织(P<0.05)。结论:肾母细胞瘤IGF-2外显子9去甲基化可能是引起IGF双等位基因表达,进一步导致肿瘤的发生发展的确切机制,从肾母细胞瘤的发生发展分子机制方面为肾母细胞瘤的早期诊断和治疗提供新的理论依据。

Objective： To explore the relationship between the methylated status of 1GF-2 exon 9 and the expression of IGF-2 gene and to investigate the mechanism of IGF-2 exon 9 CpG island methylation in Wilms tumor. Methods： The IGF-2 exon 9 methylation status and IGF2 gene expression in 42 tissue samples of Wilms tumor and corresponding normal tissue were detected by methylation-sensitive restriction enzyme PCR （ MSP ） and allele-specific 1GF2 gene expression analysis. Results： The rate of IGF-2 exon 9 methylation was 16.6% in Wilms tumor tissue samples and 95.23% in normal tissue, with a significant difference （ P 〈 0.01 ）. The rate of IGF-2 exon 9 methylation was significantly different among different pathological types （ P 〈 0.01 ）. Biallelic expression of the IGF-2 in exon 9 unmethylated tissue was significantly higher than in tissue with exon 9 methylation （ P 〈 0.05 ）. Conclusion： IGF-2 exon 9 unmethylation may be the cause of biallelic expression of the IGF and may involve Wilms tumorigenesis. IGF-2 exon 9 plays an important role in regulating the proliferation andddifferentiation theoretical basis lbr early diagnosis and treatment. of nephroblastoma. The molecular mechanisms of Wilms tumor offer atheoretical basis for early diagnosis and treatment.