Abstract
Epigenetic dysregulation, including aberrant methylation of cytosine residues in DNA, is a hallmark of cancer and clearly results in oncogenic cellular alterations such as transcriptional attenuation of tumor suppressors and genomic instability. A number of studies have examined DNA methylation alterations in patients with acute myeloid leukemia (AML) and have shown that analysis of multilocus methylation patterns can identify biologically distinct AML subclasses and can predict patient prognosis. In order to utilize the prognostic capability of methylation analysis in a clinical setting, we have developed a microsphere-based HpaII tiny fragment enrichment by ligation-mediated PCR (xMELP) assay to interrogate the methylation state of genomic multiple loci along with a random forest-based classification algorithm that correlates DNA methylation status with patient prognosis. These tools can be easily implemented in a clinical molecular pathology laboratory and can be utilized for more accurate risk stratification of AML patients.
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Acknowledgments
M. Luskin, NIH T32 cancer epidemiology grant CA 09679-22; G. Wertheim, pilot project grant from the Perelman School of Medicine Hematologic Malignancies Translational Center of Excellence, grant IRG-78-002-35 from the American Cancer Society, and National Institutes of Health (1R21CA185365-01); M. Carroll, National Institutes of Health (1R21CA185365-01, 1R01CA149566-01A1, and 5R21CA185365-02), Veterans Affairs Administration (1I01BX000918-01); S.R. Master, National Institutes of Health (1R21CA185365-01). This project was supported in part by the UPenn Institute for Translational Medicine and Therapeutics (ITMAT) through a grant from the National Center for Research Resources, Grant UL1RR024134 (now at the National Center for Advancing Translational Sciences, Grant UL1TR000003).
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Wertheim, G.B.W., Luskin, M.R., Carroll, M., Master, S.R. (2017). Microsphere-Based Assessment of DNA Methylation for AML Prognosis. In: Fortina, P., Londin, E., Park, J., Kricka, L. (eds) Acute Myeloid Leukemia. Methods in Molecular Biology, vol 1633. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7142-8_8
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DOI: https://doi.org/10.1007/978-1-4939-7142-8_8
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