Abstract 837: Circulating cell-free DNA methylation assay: Towards early detection of multiple cancer types

Abstract Background: Alterations in DNA methylation play a key role in tumor initiation, and methylation markers are well established for detecting various cancer types. Cancer-specific DNA methylation patterns of cell-free DNA (cfDNA) isolated from blood samples is a non-invasive method to obtain representative epigenetic information from solid tumors. In the present study, we identified and validated cancer-specific methylation markers for diagnosis of liver, breast and colorectal cancers with high sensitivity and specificity. Methods: Three blinded validation studies were performed in order to evaluate individual panels of DNA methylation markers developed for the detection of liver, breast or colorectal cancers. For the liver cancer panel study, samples drawn from 154 subjects were analyzed, including healthy donors (30) and subjects diagnosed with benign liver disease (10), liver cancer stage I-IV (60), or another cancer type (30). For the breast cancer panel study, samples drawn from 151 subjects were analyzed, including healthy donors (39) and subjects diagnosed with benign breast disease (15), breast cancer stage I-IV (65), or another cancer type (32). For the colorectal cancer panel study, samples drawn from 154 subjects were analyzed, including healthy donors (42) and subjects diagnosed with benign colorectal disease (14), colorectal cancer stage I-IV (68), or another cancer type (30). Cell-free DNA was extracted from all samples, bisulfite converted, and DNA methylation was quantified at target sites by using the IvyGene Platform for each of the three cancer-specific marker panel. Results: By quantifying DNA methylation at the target sites, the cancer-specific markers were able to differentiate subjects diagnosed with cancer from both healthy donors and subjects with benign diseases. The liver cancer cfDNA methylation panel showed an overall sensitivity of 95% and specificity of 97.5%. Whereas, the breast cancer cfDNA methylation panel correctly identified the breast cancer samples for an overall calculated sensitivity of 89% and specificity of 96%. The colorectal cancer cfDNA methylation panel also showed high overall sensitivity of 93% and specificity of 100%. Conclusions: These results demonstrate the high diagnostic potential of cfDNA methylation markers isolated from blood for the detection of multiple cancers at various stages with high sensitivity and specificity. In addition, a quantitative analysis of cfDNA methylation signature provides an opportunity for monitoring of disease. The benefits of a sensitive and specific assay to identify and monitor cancer is anticipated to aid disease management and ultimately, improve patient outcomes. Citation Format: Dhruvajyoti Roy, David Taggart, Lianghong Zheng, Dan Liu, Gen Li, Mingzhen Li, Kang Zhang, Richard A. Van Etten. Circulating cell-free DNA methylation assay: Towards early detection of multiple cancer types [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2019; 2019 Mar 29-Apr 3; Atlanta, GA. Philadelphia (PA): AACR; Cancer Res 2019;79(13 Suppl):Abstract nr 837.