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Association of Clinical Epidemiologic Exposures and Overall Survival with Genome-Wide DNA Methylation Profiles in Acute Myeloid Leukemia: Analysis of the Mayo Clinic AML Epidemiology Cohort

Background: We previously demonstrated that putative clinical epidemiologic exposures associated with leukemia risk are prevalent among AML patients, and some are associated with unique cytogenetic risk group and with clinical phenotype (Finn, Cancer Epidemiol, 2015). Herein, we studied genome-wide...

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Published in:Blood 2018-11, Vol.132 (Supplement 1), p.3987-3987
Main Authors: Torres-Gutierrez, César J., Heckman, Michael G., Hlady, Ryan A., Ketterling, Rhett P., Sproat, Lisa Z., Pearce, Kathryn E., Lesser, Elizabeth R., Diehl, Nancy N., Finn, Laura E., Jiang, Liuyan Jennifer, Robertson, Keith D., Cerhan, James R., Foran, James M.
Format: Article
Language:English
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Summary:Background: We previously demonstrated that putative clinical epidemiologic exposures associated with leukemia risk are prevalent among AML patients, and some are associated with unique cytogenetic risk group and with clinical phenotype (Finn, Cancer Epidemiol, 2015). Herein, we studied genome-wide DNA methylation in a cohort of AML patients to evaluate the association of individual hyper- and hypo-methylated CpG sites with epidemiologic exposures and overall survival. Methods: The Mayo Clinic AML Epidemiology Cohort is a highly annotated retrospective case series of 295 consecutive patients (pts) with AML diagnosed and treated at Mayo Clinic Florida and Arizona, with central cytogenetics performed in all cases. The prevalence of clinical epidemiologic exposures, past medical and family history as well as medication use and lifestyle was systematically obtained. After IRB approval, we interrogated the cytogenetic database and successfully obtained leukemia DNA from available remnant diagnostic cytogenetic cell pellets in a cohort of 148 AML patients in the Mayo epidemiology case series and performed an assessment of genome-wide DNA methylation using the Infinium HumanMethylation450K BeadChip. Samples were processed using the R Bioconductor package ‘minfi’ using Subset Within Array Quantile Normalization (PMID: 22703947). Individual CpGs that did not reach a detection p-value of
ISSN:0006-4971
1528-0020
DOI:10.1182/blood-2018-99-119386