Department of Medical Oncology, Dana-Farber Cancer Institute, Boston, MA, USA.
Center for Functional Cancer Epigenetics, Dana-Farber Cancer Institute, Boston, MA, USA.
Nat Med. 2023 Nov;29(11):2737-2741. doi: 10.1038/s41591-023-02605-z. Epub 2023 Oct 21.
Although circulating tumor DNA (ctDNA) assays are increasingly used to inform clinical decisions in cancer care, they have limited ability to identify the transcriptional programs that govern cancer phenotypes and their dynamic changes during the course of disease. To address these limitations, we developed a method for comprehensive epigenomic profiling of cancer from 1 ml of patient plasma. Using an immunoprecipitation-based approach targeting histone modifications and DNA methylation, we measured 1,268 epigenomic profiles in plasma from 433 individuals with one of 15 cancers. Our assay provided a robust proxy for transcriptional activity, allowing us to infer the expression levels of diagnostic markers and drug targets, measure the activity of therapeutically targetable transcription factors and detect epigenetic mechanisms of resistance. This proof-of-concept study in advanced cancers shows how plasma epigenomic profiling has the potential to unlock clinically actionable information that is currently accessible only via direct tissue sampling.
虽然循环肿瘤 DNA (ctDNA) 检测越来越多地用于为癌症治疗中的临床决策提供信息，但它们在识别控制癌症表型及其在疾病过程中动态变化的转录程序方面能力有限。为了解决这些局限性，我们开发了一种从 1 毫升患者血浆中全面进行癌症表观基因组分析的方法。我们使用针对组蛋白修饰和 DNA 甲基化的免疫沉淀方法，在 433 名患有 15 种癌症之一的个体的血浆中测量了 1,268 种表观基因组谱。我们的检测提供了转录活性的可靠替代指标，使我们能够推断诊断标志物和药物靶点的表达水平，测量治疗靶点转录因子的活性，并检测耐药的表观遗传机制。这项在晚期癌症中的概念验证研究表明，血浆表观基因组分析有可能揭示目前只能通过直接组织采样获得的临床可操作信息。
