A serum-based DNA methylation assay provides accurate detection of glioma

Background. The detection of somatic mutations in cell-free DNA (cfDNA) from liquid biopsy has emerged as a noninvasive tool to monitor the follow-up of cancer patients. However, the significance of cfDNA clinical utility remains uncertain in patients with brain tumors, primarily because of the limited sensitivity cfDNA has to detect real tumor-specific somatic mutations. This unresolved challenge has prevented accurate follow-up of glioma patients with noninvasive approaches. Methods. Genome-wide DNA methylation profiling of tumor tissue and serum cfDNA of glioma patients. Results. Here, we developed a noninvasive approach to profile the DNA methylation status in the serum of patients with gliomas and identified a cfDNA-derived methylation signature that is associated with the presence of gliomas and related immune features. By testing the signature in an independent discovery and validation cohorts, we developed and verified a score metric (the glioma-epigenetic liquid biopsy score or GeLB) that optimally distinguished patients with or without glioma (sensitivity: 100%, specificity: 97.78%). Furthermore, we found that changes in GeLB score reflected clinicopathological changes during surveillance (eg, progression, pseudoprogression, and response to standard or experimental treatment). Conclusions. Our results suggest that the GeLB score can be used as a complementary approach to diagnose and follow up patients with glioma.

Automated summary

A noninvasive approach was developed to profile DNA methylation status in the serum of glioma patients and identified a cfDNA-derived methylation signature associated with the presence of gliomas and related immune features. By testing in independent cohorts, a GeLB score was developed and verified that could distinguish patients with or without glioma effectively, with changes in GeLB score reflecting clinicopathological changes during surveillance.