Rainier S, Dobry C J, Feinberg A P
Department of Medicine, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA.
Cancer Res. 1995 May 1;55(9):1836-8.
We and others have described loss of imprinting (LOI) of the insulin-like growth factor II (IGF2) gene in 70% of Wilms' tumors (WT), an embryonal kidney tumor, and we have also found LOI of the H19 gene in 29% of WTs. In WT, LOI of IGF2 is coupled to down-regulation of H19. LOI of IGF2 has subsequently been described in a second embryonal neoplasm, rhabdomyosarcoma. However, the hypothesis that LOI is a general feature of embryonal tumors is challenged by a report of absence of LOI in three hepatoblastomas (S. M. Davies, Cancer Res., 53: 4781-4783, 1993). We identified five hepatoblastomas informative for a transcribed polymorphism of the IGF2 gene. One tumor showed LOI of IGF2, in contrast to the previous report. That tumor also showed LOI of H19, further documenting a role for this gene in imprinting disturbances in cancer. However, in contrast to WT, LOI in hepatoblastoma was not associated with down-regulation of H19. Thus, IGF2 and H19 expression can be uncoupled in tumors with LOI.
我们和其他研究人员曾报道,在70%的肾母细胞瘤(WT,一种胚胎性肾肿瘤)中,胰岛素样生长因子II(IGF2)基因存在印记缺失(LOI)现象,并且我们还发现,29%的肾母细胞瘤中存在H19基因的LOI。在肾母细胞瘤中,IGF2的LOI与H19的下调相关。随后,在第二种胚胎性肿瘤横纹肌肉瘤中也发现了IGF2的LOI。然而,有报告称三例肝母细胞瘤中不存在LOI(S.M.戴维斯,《癌症研究》,53:4781 - 4783,1993),这对LOI是胚胎性肿瘤的普遍特征这一假说提出了挑战。我们鉴定出五例对IGF2基因转录多态性具有信息价值的肝母细胞瘤。与之前的报告不同,其中一例肿瘤显示出IGF2的LOI。该肿瘤还显示出H19的LOI,进一步证明了该基因在癌症印记紊乱中的作用。然而,与肾母细胞瘤不同的是,肝母细胞瘤中的LOI与H19的下调无关。因此,在存在LOI的肿瘤中,IGF2和H19的表达可能会解偶联。