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

点击翻译按钮获取中文摘要

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.