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LINE-1methylation in plasma DNA as a biomarker of activity of DNA methylation inhibitors in patients with solid tumors
| Content Provider | Scilit |
|---|---|
| Author | Aparicio, Ana Barske, Lindsey Wang, Xuemei Bollati, Valentina Weisenberger, Daniel Yoo, Christine Tannir, Nizar Horne, Erin Groshen, Susan Jones, Peter M. Yang, Allen S. Issa, Jean-Pierre |
| Copyright Year | 2009 |
| Description | 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 compared four methods to measure LINE-1 and MAGE-A1 promoter methylation in T24 and HCT116 cancer cells treated with decitabine treatment and selected Pyrosequencing for its greater reproducibility and higher signal to noise ratio. 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. Ongoing studies will determine whether changes in LINE-1 methylation in plasma DNA occur as a result of treatment with DNA methylation inhibitors and parallel changes in tumor tissue DNA. |
| Related Links | https://www.tandfonline.com/doi/pdf/10.4161/epi.4.3.8694?needAccess=true https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2848123/pdf |
| Ending Page | 184 |
| Page Count | 9 |
| Starting Page | 176 |
| ISSN | 15592294 |
| e-ISSN | 15592308 |
| DOI | 10.4161/epi.4.3.8694 |
| Journal | Epigenetics |
| Issue Number | 3 |
| Volume Number | 4 |
| Language | English |
| Publisher | Informa UK Limited |
| Publisher Date | 2009-04-30 |
| Access Restriction | Open |
| Subject Keyword | Journal: Epigenetics Medical Laboratory Technology Dna Methylation Plasma Dna Biomarker Cancer Repetitive Elements Dna Methylation Inhibitors Solid Tumors Repetitive Dna Elements Line Mage-a1 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Medicine Molecular Biology Cancer Research |
