血浆中的无细胞DNA（cfDNA）可以与含有表观遗传修饰的核小体结合，代表细胞来源的表观遗传图谱。其中包括组蛋白H3-赖氨酸36三甲基化（H3K36me3），是活性转录的标志。我们假设在血浆中H3K36me3修饰的核小体进行无细胞染色质免疫共沉淀（cfChIP），可以描绘出肿瘤基因表达水平。我们对非小细胞肺癌病人（NSCLC，n = 8），小细胞肺癌病人（SCLC，n = 4）以及健康对照组（n = 4）的血浆样品进行了H3K36me3 cfChIP-seq，然后进行了定向NGS。 H3K36me3 cfChIP-seq表明，与正常等位基因相比，已知体细胞突变的患者血浆中突变等位基因的富集度有所增加。此外，在SCLC和NSCLC肿瘤中鉴定的基因在NSCLC和SCLC血浆中的H3K36me3 cfChIP富集度比较中具有一致性（灵敏度为0.80和0.86）。本文的发现扩展了液体活检中cfDNA的实用性，可以用于表征耐药性、癌症分型和疾病进展。本文受版权保护。保留所有权利。

Cell-free DNA (cfDNA) in blood plasma can be bound to nucleosomes that contain post-translational modifications representing the epigenetic profile of the cell of origin. This includes histone H3 lysine 36 trimethylation (H3K36me3), a marker of active transcription. We hypothesized that cell-free chromatin immunoprecipitation (cfChIP) of H3K36me3-modified nucleosomes present in blood plasma can delineate tumor gene expression levels. H3K36me3 cfChIP followed by targeted NGS (cfChIP-seq) was performed on blood plasma samples from non-small cell lung cancer patients (NSCLC, n = 8), small cell lung cancer patients (SCLC, n = 4) and healthy controls (n = 4). H3K36me3 cfChIP-seq demonstrated increased enrichment of mutated alleles compared to normal alleles in plasma from patients with known somatic cancer mutations. Additionally, genes identified to be differentially expressed in SCLC and NSCLC tumors had concordant H3K36me3 cfChIP enrichment profiles in NSCLC (sensitivity = 0.80) and SCLC blood plasma (sensitivity = 0.86). Findings here expand the utility of cfDNA in liquid biopsies to characterize treatment resistance, cancer subtyping, and disease progression.This article is protected by copyright. All rights reserved.