Shiraishi M, Sekiya T
Oncogene Division, National Cancer Center Research Institute, Tokyo.
Jpn J Cancer Res. 1989 Oct;80(10):924-7. doi: 10.1111/j.1349-7006.1989.tb01627.x.
Loss of heterozygosity at several chromosomal loci is frequently observed in human cancers and loss of one allele is supposed to affect expression of the gene(s) in the remaining allele. As DNA methylation is known to be closely related to gene expression in vertebrates, we are interested in the methylation status of the regions of alleles remaining after loss of their counterparts. In this work we investigated the methylation status of DNA from human lung carcinoma in which heterozygosity was lost at 3p and 13q and found that the remaining allele at these loci was preferentially demethylated. In contrast, tumor DNAs without allele loss tended to retain highly methylated states. These results suggest that in tumors, change of the DNA methylation status is closely related with allele loss, and vice versa.
在人类癌症中经常观察到几个染色体位点的杂合性缺失,并且一个等位基因的缺失被认为会影响其余等位基因中基因的表达。由于已知DNA甲基化与脊椎动物的基因表达密切相关,我们对其对应等位基因缺失后剩余等位基因区域的甲基化状态感兴趣。在这项研究中,我们调查了在3p和13q处杂合性缺失的人肺癌DNA的甲基化状态,发现这些位点的剩余等位基因优先去甲基化。相反,没有等位基因缺失的肿瘤DNA倾向于保持高度甲基化状态。这些结果表明,在肿瘤中,DNA甲基化状态的改变与等位基因缺失密切相关,反之亦然。