Abstract A10: Glioma cell-free DNA methylation marker for diagnosis and monitoring

Abstract

Abstract Genome-wide DNA-methylation profiling has shown that epigenetic abnormalities are biologically and clinically important signs in glioma and can be used to classify these tumors into distinct prognostic groups. Thus far, DNA methylation profiling of gliomas has required surgically resected tissue. Because gliomas release tumoral material into biofluids, such as blood, we developed a method using a liquid biopsy (LB) for minimally invasive surveillance of the tumor. We performed a genome-wide CpG methylation profile of cell-free DNA extracted from serum of patients with primary glioma (N=48) and during clinical follow-up (N=33). We used a supervised machine learning (ML) approach to identify glioma-specific epigenetic signatures in the LB (eLB) (N=1000, false-discovery rate < 0.003) to distinguish patients with glioma from those without glioma. The epigenetic profiles of matched tumor tissue showed that there was 67% concordance between the eLB signatures of the glioma in serum and tissue. Using these signatures as input for ML, we derived the glioma epigenetic liquid biopsy (GeLB) score. An independent validation study (68 gliomas and 65 nongliomas) showed that a GeLB score ≥ 50% could predict with 96% accuracy (sensitivity = 97.1% and specificity = 95.9%) whether a patient had glioma or not. Changes in GeLB score also reflected clinicopathologic changes observed during surveillance (e.g., progression, pseudoprogression, or response to a clinical trial drug). Our results suggest that the GeLB score could be used as a complementary approach to diagnose glioma and follow up patients postsurgically. Finally, we provide an online tool for predicting glioma based on the cell-free DNA methylome (hbtc.shinyapps.io/GeLB/). Citation Format: Thais Sabedot, Tathiane Malta, James Snyder, Kevin Nelson, Michael Wells, Ana deCarvalho, Abir Mukherjee, Dhan Chitale, Maritza Mosella, Karam Asmaro, Adam Robin, Mark Rosenblum, Tom Mikkelsen, Jack Rock, Laila Poisson, Ian Lee, Tobias Walbert, Steven Kalkanis, Ana Valeria Castro, Houtan Noushmehr. Glioma cell-free DNA methylation marker for diagnosis and monitoring [abstract]. In: Proceedings of the AACR Special Conference on Advances in Liquid Biopsies; Jan 13-16, 2020; Miami, FL. Philadelphia (PA): AACR; Clin Cancer Res 2020;26(11_Suppl):Abstract nr A10.