Identification of clinical implications and potential prognostic models of chromatin regulator mutations in multiple myeloma

作者：Lina Zhang, Run Zhang, Jing Wang, Ying Chen, Chun Qiao, Qinglin Shi, Yuanyuan Jin, Xuxing Shen, Jianyong Li, Lijuan Chen · 发表于：Clinical Epigenetics · 年份：2022 · DOI：10.1186/s13148-022-01314-7 · 被引用次数：11 · 研究领域：Multiple Myeloma Research and Treatments、Chromatin Remodeling and Cancer、Protein Degradation and Inhibitors

Abstract Background With the rapid development of next-generation sequencing (NGS) technologies, researchers are making efforts to reveal the genomic landscape of multiple myeloma (MM). However, the clinical significance of many mutations remains poorly defined due to the genetic heterogeneity of MM. To systematically explore the clinical implications of gene mutations and build practical prognostic models, we performed DNA sequencing in newly diagnosed MM patients. Methods MM cells were purified from bone marrow aspirates using CD138 microbeads and subjected to sequencing with a 387-gene Panel. Nomogram was developed using Cox’s proportional hazards model, and candidate variables were screened by stepwise regression. Internal validation was carried out by the bootstrap method. Results Between July 2016 and December 2020, a total of 147 patients were included in our study. We found patients with a higher mutational load had a significantly shorter progress-free survival (PFS) (19.0 vs. 32.0 months, P = 0.0098) and overall survival (OS) (3-year OS rates were 66.1% and 80.0%, P = 0.0290). Mutations in chromatin regulators (CRs) including KMT2C (14.3%), KMT2D (14.3%), EP300 (11.6%) and ARID gene family (31.3%) were highly frequent in newly diagnosed MM patients. Interestingly, proteins encoded by these genes could form a complex called KMT2C/D COMPASS (KCDCOMs). Patients with mutations of ARID gene family had a significantly shorter PFS (15.5 vs. 34.0 months, P = 0.0003) and OS ...