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

每三个人中就有一个会患癌症。然而，近年来，早期发现和最新一代疗法大大提高了确诊患者的生存率。现在，在很多情况下，癌症被认为是一种慢性病。即使经过有效的治疗，也会发生复发，主要是由残留的恶性细胞存活引起的。治疗后剩余癌细胞的定量（最小残留疾病，MRD）是确定癌症患者的反应水平和临床结果的有力工具。下一代测序（NGS）用于MRD监测是一种新的可靠方法。尽管这项技术具有很高的敏感性和临床影响，但某些癌症亚型的正确生物标志物仍然未知。体细胞基因突变、基因重排、表观遗传改变和结构变异等遗传标记的表征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这些疾病。该项目将侧重于血液学和实体肿瘤。液体活检监测（血液测试）将扩大，新的策略来监测MRD，如DNA甲基化或结构变异跟踪将被探索。将建立新的游离细胞（cfDNA）纯化和测序方案，以定义一个实验管道，通过深度亚硫酸氢盐测序（DBS）的DNA甲基化特征来量化外周血中的MRD，并通过纳米孔长读测序来定义结构变异序列。

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.