Mutation analysis of 77 patients with normal-karyotype myelodysplastic syndrome
10.3760/cma.j.issn.1003-9406.2019.09.001
- VernacularTitle: 正常核型骨髓增生异常综合征患者的基因变异谱系分析
- Author:
Wei QIN
1
,
2
;
Meiyu CHEN
;
Xiaohui CAI
;
Hongying CHAO
;
Jie LIU
;
Naike JIANG
;
Min ZHOU
;
Xuzhang LU
;
Suning CHEN
;
Ri ZHANG
;
Chuan HE
;
Qian WANG
Author Information
1. Department of Hematology, the Affiliated Changzhou Second Hospital of Nanjing Medical University, Changzhou, Jiangsu 213003, China
2. Jiangsu Provincial Institute of Hematology, Key Laboratory of Thrombosis and Hemostasis of the Ministry of Health, the First Affiliated Hospital of Suzhou University, Suzhou, Jiangsu 215006, China
- Publication Type:Journal Article
- Keywords:
Myelodysplastic syndromes;
Gene landscape;
Normal karyotype
- From:
Chinese Journal of Medical Genetics
2019;36(9):857-861
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To carry out mutation analysis for patients with myelodysplastic syndromes (MDS) and a normal karyotype.
Methods:Targeted capture and next-generation sequencing (NGS) was carried out using a customized 49-gene panel. FLT3 internal tandem duplication (FLT3-ITD), CALR, NPM1 and CEBPA mutations were detected by PCR and Sanger sequencing.
Results:Sixty two patients (80.5%) were found to harbor at least one mutation. Each patient has carried 2.21 mutations in average. Coexistence of ≥ 3 mutations was common (43.7%). The most commonly mutated genes were RUNX1 (23.4%, 18/77), ASXL1 (18.2%, 14/77), NPM1 (15.6%, 12/77), U2AF1 (15.6%, 12/77), DNMT3A (11.7%, 9/77). Patients with SF3B1 mutations were significantly older than those with ASXL1 mutations (P=0.023). Mutations of the DNMT3A gene were significantly associated with the blood platelet level compared with BCOR mutations (P=0.02). No significant difference was found in the number and rate of mutations between those under or above 60-year-old. Among 67 patients with clinical follow-up, 20 (29.8%) has transformed to acute myeloid leukemia, and the time of transformation has ranged from 1 to 44 months, with a average of 5.3 months. RUNX1, U2AF1 and FLT3 mutations are associated with leukemic transformation.
Conclusion:Coexistence of ≥ 3 mutations are frequent among patients with normal-karyotype MDS. Certain mutations are associated with age and leukemic transformation.
