IgM 型多发性骨髓瘤的综合基因组分析确定 IRF4 为预后标志物。

Comprehensive genomic profiling of IgM multiple myeloma identifies IRF4 as a prognostic marker.

作者信息

Ryu Daeun, Kim Hee Jin, Joung Je-Gun, Lee Hae-Ock, Bae Joon Seol, Kim Seok Jin, Kim Haesu, Park Woong-Yang, Kim Kihyun

机构信息

Samsung Genome Institute, Sungkyunkwan University School of Medicine, Seoul, Korea.

Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea.

出版信息

Oncotarget. 2016 Jul 26;7(30):47127-47133. doi: 10.18632/oncotarget.9478.

DOI:10.18632/oncotarget.9478

PMID:27223072

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5216929/

Abstract

Immunoglobulin M multiple myeloma (IgM MM) is an extremely rare subtype of multiple myeloma with a poor clinical outcome. In this study, bone marrow aspirates of MM patients, including two cases of IgM MM, were analyzed by whole exome sequencing and RNA sequencing. Recurrent somatic mutations in the NRAS, KRAS, CCND1, DIS3, and TP53 genes were found in IgM MM and other types of MM, in agreement with previous studies. Overall transcription profiles of IgM and other types of MM clustered together, but separate from normal blood or peripheral plasma cells. Among the differentially expressed genes in IgM MM, IRF4 was highly expressed in IgM as well as in a subset of other types of MM patients. Thus, IRF4 is an independent prognostic factor for general MM patients. Taken together, the somatic mutation and transcriptome profiles support the idea that IgM MM can be classified as an aggressive MM subtype.

摘要

免疫球蛋白M多发性骨髓瘤（IgM MM）是多发性骨髓瘤中极为罕见的一种亚型，临床预后较差。在本研究中，通过全外显子组测序和RNA测序对包括两例IgM MM患者在内的骨髓瘤患者骨髓穿刺样本进行了分析。在IgM MM和其他类型的骨髓瘤中发现了NRAS、KRAS、CCND1、DIS3和TP53基因的复发性体细胞突变，这与之前的研究结果一致。IgM和其他类型骨髓瘤的整体转录谱聚集在一起，但与正常血液或外周浆细胞分开。在IgM MM中差异表达的基因中，IRF4在IgM以及其他类型骨髓瘤患者的一个亚组中高表达。因此，IRF4是一般骨髓瘤患者的独立预后因素。综上所述，体细胞突变和转录组谱支持IgM MM可被归类为侵袭性骨髓瘤亚型这一观点。