Multiplexed, single-molecule, epigenetic analysis of plasma-isolated nucleosomes for cancer diagnostics
Menée notamment à partir d'échantillons plasmatiques prélevés sur des témoins sains et des patients atteints d'un cancer colorectal, pulmonaire, pancréatique ou mammaire, cette étude met en évidence la performance d'un test multiparamétrique, utilisant l'imagerie de fluorescence et basé sur le profil épigénétique des nucléosomes, la méthylation de l'ADN libre circulant ou des biomarqueurs spécifiques des cancers, pour détecter différents types tumoraux
The analysis of cell-free DNA (cfDNA) in plasma provides information on pathological processes in the body. Blood cfDNA is in the form of nucleosomes, which maintain their tissue- and cancer-specific epigenetic state. We developed a single-molecule multiparametric assay to comprehensively profile the epigenetics of plasma-isolated nucleosomes (EPINUC), DNA methylation and cancer-specific protein biomarkers. Our system allows for high-resolution detection of six active and repressive histone modifications and their ratios and combinatorial patterns on millions of individual nucleosomes by single-molecule imaging. In addition, our system provides sensitive and quantitative data on plasma proteins, including detection of non-secreted tumor-specific proteins, such as mutant p53. EPINUC analysis of a cohort of 63 colorectal cancer, 10 pancreatic cancer and 33 healthy plasma samples detected cancer with high accuracy and sensitivity, even at early stages. Finally, combining EPINUC with direct single-molecule DNA sequencing revealed the tissue of origin of colorectal, pancreatic, lung and breast tumors. EPINUC provides multilayered information of potential clinical relevance from limited (<1 ml) liquid biopsy material.
Nature Biotechnology , résumé, 2022