Establishment of a reliable, efficient, and comprehensive approach to mutation analysis in myelodysplastic syndromes

骨髓增生异常综合征（MDS）是一种异质组造血干细胞疾病。他们的特点是两个主要特征：无效的造血导致骨髓衰竭和倾向于转化为急性髓性白血病（AML）。MDS的病理生理学是复杂的，仍然知之甚少。目前的疾病机制概念包括基因突变导致细胞增殖、成熟和存活调节异常。MDS中发生突变的基因包括TET2、ASXL1、RUNX1、NRAS、KRAS、EZH2、DNMT3A、IDH1、IDH2、p53、ETV6和CBL。其中一些突变对患者的总体生存有负面影响，如ASXL1、EZH2、RUNX1、ETV6和TP53。随着MDS中突变基因数量的稳步增加，迫切需要新的方法来处理大量的分析。这种测序方法的必要条件包括高灵敏度和特异性（用于识别正确的突变）、高效率（用于筛选大量患者的许多基因）和成本效益。5500固体测序系统有潜力满足测序系统的所有要求。然而，这种新系统尚未在MDS突变分析中进行高通量测序测试。这个项目的目标是测试和建立5500固体系统作为一种新的、高效的、经济的高通量测序技术，用于MDS患者的突变分析。

Myelodysplastic syndromes (MDS) are a heterogeneous group of hematopoietic stem cell disorders. They are characterized by two cardinal features: ineffective hematopoiesis leading to marrow failure and a propensity to transform to acute myeloid leukemia (AML). The pathophysiology of MDS is complex and remains poorly understood. The current concept of the disease mechanism includes mutations in genes leading to abnormalities in the regulation of cellular proliferation, maturation, and survival. Genes mutated in MDS include TET2, ASXL1, RUNX1, NRAS, KRAS, EZH2, DNMT3A, IDH1, IDH2, p53, ETV6, and CBL . Some of these mutations have a negative prognostic impact on overall survival for patients such as ASXL1, EZH2, RUNX1, ETV6 and TP53. As the number of mutated genes in MDS is steadily increasing, novel approaches to cope with the large number of analyses are urgently needed. The sine qua non for this sequencing approach includes high sensitivity and specificity (for identifying the correct mutations), high efficiency (for screening a large patient number for many genes), and cost effectiveness. The 5500 Solid Sequencing System has the potential to fulfill all the requirements for the sequencing system. However, this novel system has not been tested for high throughput sequencing in mutation analysis in MDS. The goal of this project is to test and establish the 5500 Solid System as a novel, efficient and cost effective high-throughput sequencing technique for mutation analysis in MDS patients.