Methylation Analysis of cfDNA IDs >50 Cancer Types

Sensitivity increased with increasing stage from 39 percent in stage I to 92 percent in stage IV
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TUESDAY, March 31, 2020 (HealthDay News) -- Methylation analysis of circulating cell-free DNA (cfDNA) sequencing can detect malignancy across stages with high specificity, according to a study published online March 30 in the Annals of Oncology.

Minetta C. Liu, M.D., from the Mayo Clinic in Rochester, Minnesota, and colleagues assessed the performance of targeted methylation analysis of cfDNA among 6,689 participants (2,428 with cancer [>50 types] and 4,207 without cancer) who were categorized into training and validation sets. Bisulfite sequencing targeting a panel of >100,000 informative methylation regions was performed on plasma cfDNA. A classifier was developed and validated for detecting cancer and localization of tissue of origin (TOO).

The researchers observed consistent performance in the training and validation sets. Specificity was 99.3 percent in the validation set. In a prespecified set of 12 cancer types, which account for about 63 percent of U.S. cancer deaths annually, stage I to III sensitivity was 67.3 percent; sensitivity was 43.9 percent in all cancer types. With increasing stage, detection increased: In the prespecified cancer types, sensitivity was 39, 69, 83, and 92 percent in stages I, II, III, and IV, respectively. In 96 percent of samples with a cancer-like signal, TOO was predicted; TOO localization was accurate in 93 percent.

"These results support the feasibility of employing this targeted methylation analysis of cfDNA in ongoing clinical trials in the intended use population for early cancer detection," the authors write.

Several authors disclosed financial ties to biopharmaceutical and biotechnology companies, including GRAIL, which funded the study.

Abstract/Full Text

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