Analysis of common gene mutations in patients with myelodysplastic syndromes in lower-risk and higher-risk groups
10.3760/cma.j.cn115356-20231214-00105
- VernacularTitle:较低危组与较高危组骨髓增生异常综合征患者常见基因突变分析
- Author:
Jiangnan LIU
1
;
Baoan CHEN
;
Jiao ZHOU
;
Jian CHENG
Author Information
1. 东南大学附属中大医院血液科，南京 210009
- Keywords:
Myelodysplastic syndromes;
Risk assessment;
Gene mutations;
Revised International Prognostic Scoring System
- From:
Journal of Leukemia & Lymphoma
2024;33(7):399-404
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the differences in gene mutations and functional clusters of gene mutations in patients with myelodysplastic syndromes (MDS) in the lower-risk and higher-risk groups.Methods:A retrospective case series study was conducted. Clinical data of 227 patients with MDS in Zhongda Hospital of Southeast University from January 2018 to August 2023 were retrospectively analyzed. According to the Revised International Prognostic Scoring System (IPSS-R), MDS patients were categorized into the lower-risk group (IPSS-R score ≤3.5 points, 96 cases) and the higher-risk group (IPSS-R score >3.5 points, 131 cases). Bone marrow specimens were tested for mutations of 58 common MDS genes using next-generation sequencing, and the 24 genes with the high mutation rates were included in the study, and the 24 mutated genes were categorized into 8 clusters according to gene function. The differences in clinical data, gene mutations and gene mutation functional clusters were compared between the lower-risk group and the higher-risk group.Results:At least 1 gene mutation was detected in 177 (78.0%) of 227 MDS patients, of which the 5 genes with high mutation rates were ASXL1 [21.6% (49/227)], TET2 [18.5% (42/227)], TP53 [15.4% (35/227)], DNMT3A [13.2% (30/227)], and U2AF1 [10.1% (23/227)] in turn. By gene function analysis, the most common mutation cluster was methylation-related genes [31.3% (71/227)], followed by spliceosome-related genes [24.7% (56/227)]. Platelet count and neutrophil count in the lower-risk group were higher than those in the higher-risk group, and the proportion of bone marrow primitive cells, the mutation rate and the presence of ≥3 mutations were lower than those in the higher-risk group (all P < 0.05). The 5 genes with high mutation rates in the lower-risk group were TET2 [21.9% (21/96)], DNMT3A [14.6% (14/96)], ASXL1 [13.5% (13/96)], SF3B1 [12.5% (12/96)], and U2AF1 [8.3% (8/96)] in turn. The 5 genes with high mutation rates in the higher-risk group were ASXL1 [27.5% (36/131)], TP53 [23.7% (31/131)], TET2 [16.0% (21/131)], DNMT3A [12.2% (16/131)], and U2AF1 [11.5% (15/131)] in turn, and the mutation rates of ASXL1, TP53, ETV6, and NRAS genes in the lower-risk group were lower than those in the higher-risk group (all P < 0.05). The mutation rate of methylation-related genes was the highest in both the lower-risk group and the higher-risk group, but the difference between the two groups was not statistically significant [32.3% (31/96) vs. 30.5% (40/131), χ2 = 0.08, P>0.05]. The differences in the proportions of tumor factor suppressor-related genes, transcription factor-related genes, chromatin-modification-related genes and RAS pathway-related genes mutations between the two groups were all statistically significant (all P < 0.05). Conclusions:The higher-risk group has a higher rate of common gene mutations and a greater number of gene mutations than the lower-risk group in MDS patients.
