表观遗传学
组蛋白
DNA甲基化
胰腺癌
癌症
结直肠癌
生物
液体活检
核小体
癌症研究
DNA
胎儿游离DNA
化学
计算生物学
生物化学
遗传学
基因
基因表达
胎儿
产前诊断
怀孕
作者
Vadim Fedyuk,Nir Erez,Noa Furth,Olga Beresh,Ekaterina N. Andreishcheva,Abhijeet Shinde,Dan Jones,Barak Bar Zakai,Yael Mavor,Tamar Peretz,Ayala Hubert,Jonathan Cohen,Azzam Salah,Mark Temper,Albert Grinshpun,Myriam Maoz,Aviad Zick,G. Ron,Efrat Shema
标识
DOI:10.1038/s41587-022-01447-3
摘要
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.
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