Non-invasive multi-cancer diagnosis using DNA hypomethylation of LINE-1 retrotransposons

The detection of circulating tumor DNA, which allows non-invasive tumor molecular profiling and disease follow-up, promises optimal and individualized management of patients with cancer. However, detecting small fractions of tumor DNA released when the tumor burden is reduced remains a challenge. We implemented a new highly sensitive strategy to detect base-pair resolution methylation patterns from plasma DNA and assessed the potential of hypomethylation of LINE-1 retrotransposons as a non-invasive multi-cancer detection biomarker. Resulting machine learning-based classifiers showed powerful correct classification rates discriminating healthy and tumor plasmas from 6 types of cancers in two independent cohorts (AUC = 88% to 100%, N = 747). This should lead to the development of more efficient non-invasive diagnostic tests adapted to all cancer patients, based on the universality of these factors. One-Sentence Summary LINE-1 retrotransposons hypomethylation is a sensitive and specific biomarker to detect multiple forms of cancer non-invasively