Identification of new cancer specific genetic and epigenetic biomarkers for cancer evolution and Minimal Residual Disease (MRD) in peripheral blood samples

鉴定外周血样本中癌症进化和微小残留病 (MRD) 的新癌症特异性遗传和表观遗传生物标志物

• 批准号: 493951700
• 负责人: Dr. Larissa Haertle
• 金额: --
• 依托单位: Klinik und Poliklinik für Innere Medizin III: Hämatologie und Onkologie
• 依托单位国家: 德国
• 项目类别: WBP Fellowship
• 财政年份: 2021
• 资助国家: 德国
• 起止时间: 2020-12-31 至 2023-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/493951700?language=en
• 关键词: Identification; new; cancer; specific; genetic

Cancer will affect one in every three human beings. However early detection and latest generation therapies have substantially improved the survival of patients diagnosed in recent years. In many cases, nowadays, cancer is considered a chronic disease. And relapses occur, even after efficient treatment, mostly induced by the survival of residual malignant cells. The quantification of these cancer cells remaining after treatment (Minimal Residual Disease, MRD) is a powerful tool to define the level of response and clinical outcome of cancer patients. Next Generation Sequencing (NGS) for MRD monitoring is a new reliable approach. Despite the high sensitivity and clinical impact of this technology, the right biomarkers for some cancer subtypes are still unknown. The characterization of genetic markers such as somatic gene mutations, gene rearrangements, epigenetic alterations and structural variants in an individualised (patient specific) manner, will help patients to know the evolution of their disease and clinicians to better decide when and how to treat them. The project will be focused on hematological and solid tumours. Liquid biopsy monitoring (blood test) will be expanded and new strategies to monitor MRD such as DNA methylation or structural variants tracking will be explored. New protocols for cell-free (cfDNA) purification and sequencing will be established in order to define an experimental pipeline to quantify MRD in peripheral blood using DNA methylation signatures by Deep Bisulfite Sequencing (DBS) and defining structural variant sequences by nanopore long read sequencing.

癌症将影响每三个人中的一个。然而，近年来，早期发现和最新一代疗法大大改善了确诊患者的生存率。如今，在许多情况下，癌症被认为是一种慢性疾病。即使在有效治疗后，复发也会发生，主要是由残留的恶性细胞的存活引起的。治疗后残留的这些癌细胞的定量（微小残留病，MRD）是定义癌症患者的反应水平和临床结果的有力工具。用于MRD监测的下一代测序（NGS）是一种新的可靠方法。尽管这项技术具有高灵敏度和临床影响，但一些癌症亚型的正确生物标志物仍然未知。以个体化（患者特异性）方式表征遗传标记，如体细胞基因突变，基因重排，表观遗传改变和结构变异，将有助于患者了解其疾病的演变，并帮助临床医生更好地决定何时以及如何治疗它们。该项目将侧重于血液肿瘤和实体肿瘤。将扩大液体活检监测（血液检查），并探索监测MRD的新策略，如DNA甲基化或结构变异跟踪。将建立无细胞（cfDNA）纯化和测序的新方案，以定义实验管道，通过深度亚硫酸氢盐测序（DBS）使用DNA甲基化特征定量外周血中的MRD，并通过纳米孔长读段测序定义结构变体序列。