Prognostic mutations identified by whole-exome sequencing and validation of the Molecular International Prognostic Scoring System in myelodysplastic syndromes after allogeneic haematopoietic stem cell transplantation

IF 5.1 2区医学 Q1 HEMATOLOGY

British Journal of Haematology Pub Date : 2024-08-13 DOI:10.1111/bjh.19707

Hong Wang, Xueqian Li, Jiaqian Qi, Hong Liu, Tiantian Chu, Xiaoyan Xu, Huiying Qiu, Chengcheng Fu, Xiaowen Tang, Changgeng Ruan, Depei Wu, Yue Han

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Abstract

In 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.

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通过全外显子组测序确定的骨髓增生异常综合征异基因造血干细胞移植后的预后突变和国际分子预后评分系统的验证。

在这项研究中，我们采用全外显子组测序（WES）方法，从骨髓增生异常综合征（MDS）患者造血干细胞移植前的92份骨髓样本中获得了基因组图谱。我们在 45 个驱动基因中发现了 129 个突变。55名患者（59.8%）至少携带一个驱动基因突变。剪接因子U2AF1是队列中最常发生突变的基因（21例，23%），其次是BCOR（9例，10%）、ASXL1（8例，9%）、TET2（6例，7%）、NPM1（5例，5%）、RUNX1（5例，5%）和SETBP1（5例，5%）。WES 还在 6 个基因（PIEZO1、LOXHD1、MYH13、DNAH5、DPH1 和 USH2A）中发现了 49 个可能的致癌变异，这些变异与 MDS 移植后的总生存期（OS）或无复发生存期（RFS）相关。多变量分析显示，DNAH5和USH2A的突变是影响OS的独立风险因素。DNAH5和LOXHD1突变是导致RFS恶化的风险因素。经过多变量分析，分子国际预后评分系统对RFS仍具有独立的预后意义。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

British Journal of Haematology 医学-血液学

CiteScore

8.60

自引率

4.60%

发文量

565

审稿时长

1 months

期刊介绍： The British Journal of Haematology publishes original research papers in clinical, laboratory and experimental haematology. The Journal also features annotations, reviews, short reports, images in haematology and Letters to the Editor.