Abstract 5022: Immune biology drives cancer specific methylation profiles in blood

Blood leukocytes from patients with solid tumors exhibit complex and distinct cancer-associated patterns of DNA methylation. However, the biological mechanisms underlying these patterns remain poorly understood. Since epigenetic biomarkers offer significant clinical potential for cancer detection, we sought to address a mechanistic gap in recently published works, hypothesizing that this variation is in large part due to shifts in leukocyte populations. To discern differentially methylated regions (DMRs) among leukocyte subtypes, we assessed epigenome-wide DNA methylation in sorted, purified, healthy human peripheral blood leukocyte subtypes. Performing a targeted analysis of leukocyte DMRs from epigenome-wide blood methylation data in three independent case-control studies of different cancers revealed that leukocyte DMRs predict case status with a high degree of accuracy (area under the curve = 0.82, 0.83, and 0.67, forhead and neck squamous cell carcinoma (HNSCC), ovarian, and bladder cancer, respectively). These results demonstrate that blood-derived differences in DNA methylation patterns in patients with solid tumors are largely attributable to systematic differences in the DMRs that define specific, known leukocyte sub-populations, suggesting that the unique epigenetic signatures in blood from solid tumor patients arise as a result of immune responses represented by shifts in leukocyte populations. Citation Format: {Authors}. {Abstract title} [abstract]. In: Proceedings of the 103rd Annual Meeting of the American Association for Cancer Research; 2012 Mar 31-Apr 4; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2012;72(8 Suppl):Abstract nr 5022. doi:1538-7445.AM2012-5022