Expression silencing through CpG island methylation of DAP-kinase has been frequently found in connection with adverse survival, as cells lacking DAP-kinase appear to be more invasive and more metastatic in lung cancer.
The purpose of our study was to determine the prevalence for aberrant promoter methylation of the p16, O(6)-methylguanine-DNA methyltransferase (MGMT), death-associated protein (DAP) kinase, and Ras effector homologue (RASSFIA) genes in nonmalignant bronchial epithelial cells from current and former smokers in a hospital-based, case control study of lung cancer.
The anti-tumorigenic effect of DAP-kinase was also studied experimentally in mouse model systems where the re-introduction of DAP-kinase into highly metastatic mouse lung carcinoma cells who had lost the protein, strongly reduced their metastatic capacity.
Moreover, the groups with and without hypermethylation of the DAP kinase promoter showed a striking difference in the probability of disease-specific survival; i.e., among people who died of lung cancer-related causes specifically, the probability of 5-year survival was.56 for those with such hypermethylation and.92 for those without it (P:<.001).