Federal government websites often end in. The site is secure. Preview improvements coming to the PMC website in October Learn More or Try it out now. Multiple clinical trials are investigating the use of the DNA methylation inhibitors azacitidine and decitabine for the treatment of solid tumors. Clinical trials in hematological malignancies have shown that optimal activity does not occur at their maximum tolerated doses but selection of an optimal biological dose and schedule for use in solid tumor patients is hampered by the difficulty of obtaining tumor tissue to measure their activity.
Here we investigate the feasibility of using plasma DNA to measure the demethylating activity of the DNA methylation inhibitors in patients with solid tumors.
We then obtained DNA from plasma, peripheral blood mononuclear cells, buccal mucosa cells and saliva from ten patients with metastatic solid tumors at two different time points, without any intervening treatment. DNA methylation measurements were not significantly different between time point 1 and time point 2 in patient samples. We conclude that measurement of LINE-1 methylation in DNA extracted from the plasma of patients with advanced solid tumors, using Pyrosequencing, is feasible and has low within patient variability.
Azacitidine and decitabine, two DNA methylation inhibitors, recently obtained FDA approval for the treatment of myelodysplastic syndromes. In an effort to correlate the inhibition of DNA methylation with the clinical activity of these drugs, many investigators have sought to measure changes in DNA methylation in tumor and non-tumor tissues.
However, a variety of target sequences in DNA obtained from different tissues as well as diverse methods of measurement have been used in the different studies, leading to frequently conflicting results. For example, a decrease in p15 promoter methylation measured in bone marrow mononuclear cells by methylation-specific PCR MSP , 1 bisulfite sequencing, 1 and MsSNuPE 2 appeared to be associated with a clinical response in patients with hematological diseases, but when measured in peripheral blood mononuclear cells PBMC by COBRA, 3 and Pyrosequencing 4 , 5 this association was not found.
