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ABSTRACT: 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.
SUBMITTER: Sabedot TS
PROVIDER: S-EPMC8408843 | biostudies-literature | 2021 Sep
REPOSITORIES: biostudies-literature

Sabedot Thais S TS Malta Tathiane M TM Snyder James J Nelson Kevin K Wells Michael M deCarvalho Ana C AC Mukherjee Abir A Chitale Dhananjay A DA Mosella Maritza S MS Sokolov Artem A Asmaro Karam P KP Robin Adam A Rosenblum Mark L ML Mikkelsen Tom T Rock Jack J Poisson Laila M LM Lee Ian I Walbert Tobias T Kalkanis Steven S Iavarone Antonio A Castro Ana Valeria AV Noushmehr Houtan H
Neuro-oncology 20210901 9
<h4>Background</h4>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.<h4>Methods< ...[more]