Kondo M, Suzuki H, Ueda R, Osada H, Takagi K, Takahashi T, Takahashi T
Laboratory of Chemotherapy, Aichi Cancer Center Research Institute, Nagoya, Japan.
Oncogene. 1995 Mar 16;10(6):1193-8.
Accumulating evidence suggests that deregulation of the insulin-like growth factor II (IGF2) and H19 genes at 11p15, due to loss of imprinting (LOI), plays a role in the oncogenesis of Wilms' tumors. We previously reported LOI of IGF2 in carcinomas of the lung, a common cancer of adults. We show here that LOI of H19 is also a frequent event in lung cancer development, and correlated with hypomethylation of the promoter region. Furthermore, the present study also revealed that overexpression of H19 is often associated with LOI of H19 in lung cancers retaining both parental alleles, showing a contrast to LOI in Wilms' tumors. Interestingly, in contrast to frequent LOI of the imprinted genes at 11p15, LOI was not observed for the remaining gene known to be imprinted in man, SNRPN at 15q12.
越来越多的证据表明,由于印记丢失(LOI)导致的11p15处胰岛素样生长因子II(IGF2)和H19基因的调控异常在肾母细胞瘤的肿瘤发生中起作用。我们之前报道过IGF2在肺癌(一种常见的成人癌症)中的印记丢失。我们在此表明,H19的印记丢失在肺癌发展中也是一个常见事件,并且与启动子区域的低甲基化相关。此外,本研究还揭示,在保留双亲等位基因的肺癌中,H19的过表达通常与H19的印记丢失相关,这与肾母细胞瘤中的印记丢失形成对比。有趣的是,与11p15处印记基因频繁发生印记丢失相反,在已知在人类中印记的其余基因——15q12处的SNRPN中未观察到印记丢失。