Abstract

Epigenetics with aberrant DNA methylation is an early event in cancer development, and recent research is mainly focused on cancer-specific DNA methylations and their clinical utility in cancer detection and management. In the current study, methylation patterns of 18 overexpressed genes were observed in the cellular model (A16 and NA16) and in the circulation of tumorigenic mice to determine whether these methylation changes occur concurrently during transformation/ tumorigenesis. The results from the present study showed an enhancement of DNMT activity to 4-fold in transformed rat fibroblast cell lines in their non-adherent condition at the 16h time period. However, methylation analysis revealed only two genes out of 18, namely HIF1A and VEGFA, were amplified as methylated and unmethylated successively in both control and transformed cells. Upon transplantation into Nude mice, we observed the release of methylated HK2 and unmethylated VEGFA into the blood circulation of tumorigenic mice from weeks 1 to 11. The results confirm that HK2 & VEGFA may serve as methylated/unmethylated markers in the non-invasive detection of cancer at an early stage.

Keywords

cancer, transformed cells, tumorigenic mice, DNMTs, DNA methylation, methylated markers