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• W3032077319 abstract "5046 Background: Methylation profiling of circulating cell-free DNA (cfDNA) is a promising approach for non-invasive tumor detection due to the presence of tissue-specific epigenetic signatures that are detectable in cfDNA. Cell-free methylated DNA immunoprecipitation and high-throughput sequencing (cfMedDIP-seq) is a sensitive, low-input, cost-effective, bisulfite-free approach to profiling cfDNA methylomes, capable of detecting and classifying various tumor types. We tested the feasibility of cfMeDIP-seq to detect urothelial carcinoma (UC) in plasma samples. Methods: We performed cfMeDIP-seq on plasma samples from 43 patients (pts): 18 metastatic UC (UC) pts, 12 pre-cystectomy non-metastatic UC pts, and 13 cancer-free controls. Six (50%) of pre-cystectomy cases were non-muscle invasive UC. cfDNA was immunoprecipitated and enriched using an antibody targeting 5-methylcytosine and PCR-amplified to create a sequence-ready library. The top differentially methylated regions (DMRs) between UC and control samples were used to train a regularized binomial generalized linear model using 80% of the samples as a training set. The 20% of withheld test samples were then assigned a probability of being UC or control. This process was repeated 100 times. Results: The average amount (standard deviation) of cfDNA isolated from 1 ml of UC plasma samples was 29.2 (27.4) ng/µL and 8.02 (3.58) ng/µL in cancer-free controls. We identified 9,826 DMRs in plasma samples at an adjusted p-value of < 0.01, which partitioned UC and control samples. Iterative training and classification of held out samples using the top 300 DMRs resulted in a mean AUROC of 0.987. Conclusions: cfMeDIP-seq is an interesting new approach for non-invasive detection of UC. cfMeDIP-seq demonstrates high sensitivity to detect UC across all stages of UC, including non-muscle invasive disease." @default.
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• W3032077319 date "2020-05-20" @default.
• W3032077319 modified "2023-10-18" @default.
• W3032077319 title "Detection of urothelial carcinoma using plasma cell-free methylated DNA." @default.
• W3032077319 doi "https://doi.org/10.1200/jco.2020.38.15_suppl.5046" @default.
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