[Clinical analysis of gene mutation characteristics and mutation burden in myelodysplastic syndrome]

Objective: To investigate the relationship between gene mutation characteristics, mutation burden and general condition, disease subtype and karyotype of patients with myelodysplastic syndrome (MDS), and its clinical value. Methods: High-throughput sequencing was used to detect 65 blood tumor-related genes in 191 MDS patients and 9 secondary acute myelocytic leukemia patitents(SAML), and to analyze the characteristics of abnormal genes, mutation burden, as well as the relationship with disease subtypes, chromosome karyotypes and age. Results: Mutations were found in 148 patients (77.5%), including 47 abnormal genes and 186 mutation sites. And gene mutations were found in 9 SAML patients, the number of mutations was significantly higher than that in MDS patients (χ(2)=11.911, P=0.018). Among the abnormal genes, the mutation frequency of U2AF1 (37.3%) and ASXL1 (41.6%) were higher, and there were significant differences in mutation burden among different abnormal genes (F=91.946, P<0.001). There were differences in the number of gene mutations among different subtypes of MDS, and the number of EB-2 gene mutations was the highest (2.2±1.5). In SLD, MLD, EB-1 and EB-2, the proportion of carrying ≥ 3 mutations increased gradually (χ(2)=52.471, P=0.037). TP53 mutation was associated with abnormal karyotype (r(φ)=0.177, P=0.019), especially with complex karyotype (r(φ)=0.440, P<0.001), while NPM1 mutation is associated with normal karyotype (r(φ)=0.173, P=0.024). The number of mutations carried by patients under 30 years old was the least, and the number of mutations increased with the increase of age. The number of mutations was the most in patients aged 60 to 79 years old (P=0.017), and the mutation frequency of epigenetic related genes increased with the increase of age (P=0.041). Conclusions: The mutation characteristics and mutation load of MDS-related genes are closely related to clinical factors such as disease subtype, chromosome karyotype and patient age.