Affiliation:
1. National Clinical Research Center for Hematologic Diseases, Jiangsu Institute of Hematology The First Affiliated Hospital of Soochow University Suzhou China
2. Institute of Blood and Marrow Transplantation, Collaborative Innovation Center of Hematology Soochow University Suzhou China
3. Key Laboratory of Thrombosis and Hemostasis of Ministry of Health Suzhou China
4. State Key Laboratory of Radiation Medicine and Protection Soochow University Suzhou China
Abstract
SummaryIn this study, we used the whole‐exome sequencing (WES) approach to obtain genomic profiles from 92 marrow samples of myelodysplastic syndrome (MDS) patients before haematopoietic stem cell transplantation. We identified 129 mutations in 45 driver genes. Fifty‐five patients (59.8%) carried at least 1 driver mutation. The splicing factor U2AF1 was the most frequently mutated in the cohort (21 cases, 23%), followed by BCOR (9 cases, 10%), ASXL1 (8 cases, 9%), TET2 (6 cases, 7%), NPM1 (5 cases, 5%), RUNX1 (5 cases, 5%), and SETBP1 (5 cases, 5%). WES also identified 49 possible oncogenic variants in six genes (PIEZO1, LOXHD1, MYH13, DNAH5, DPH1, and USH2A) that were associated with overall survival (OS) or relapse‐free survival (RFS) in MDS after transplantation. Multivariate analysis showed mutations in DNAH5 and USH2A to be independent risk factors for OS. Mutations in DNAH5 and LOXHD1 were risk factors for worse RFS. The Molecular International Prognostic Scoring System retained its independent prognostic significance for RFS after multivariate analysis.
Funder
National Natural Science Foundation of China
Priority Academic Program Development of Jiangsu Higher Education Institutions