A study on the role of DNA methylation within hCG and hPL genes in trophoblastic disease

: It has been shown that the extent of methylation of cytocine in DNA is inversely correlated with gene expression in many cases. The DNAs extracted from placental tissue, hydatidiform mole and choriocarcinoma tissue were examined to see whether the extent of cytocine methylation is correlated to the gene expression of placental peptide hormones and the transformation of trophoblast. First of all we measured the amount of methylated cytocine per total DNA with HPLC. We then examined cytocine methylation in hCG alpha,beta and hPL genes using methylation sensitive (Hha I, Hpa II) and non sensitive (Msp I) restriction enzymes and molecular hybridization. During pregnancy the total amount of methylated cytocine measured with HPLC increases gradually from 0.72 mol.% at first trimester to 0.92 mol.% at term. The DNA of WBC showed a higher level of methylated cytocine than placental DNA. The extent of DNA methylation in the peptide hormone genes increases during placental development. Hypomethylation in the hCG alpha gene was also seen in molar tissue which expresses a high amount of hCG. Therefore it is inversely correlated that gene expression of hCG alpha,beta and the extent of DNA cytocine methylation. Furthermore some restriction polymorphisms were observed with Msp I in hCG alpha and hPL genes which might be related to malignant transformation of the trophoblast.