Oncotarget

Research Papers:

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

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

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Oncotarget. 2016; 7:47127-47133. https://doi.org/10.18632/oncotarget.9478

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Abstract

Daeun Ryu1,4,*, Hee Jin Kim2,*, Je-Gun Joung1,*, Hae-Ock Lee1,5, Joon Seol Bae1, Seok Jin Kim3, Haesu Kim3, Woong-Yang Park1,4,5, Kihyun Kim3

1Samsung Genome Institute, Sungkyunkwan University School of Medicine, Seoul, Korea

2Department of Laboratory Medicine & Genetics, Sungkyunkwan University School of Medicine, Seoul, Korea

3Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

4Department of Health Sciences and Technology, Samsung Advanced Institute for Health Sciences and Technology, Sungkyunkwan University School of Medicine, Seoul, Korea

5Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea

*These authors have contributed equally to this work

Correspondence to:

Kihyun Kim, email: [email protected]

Woong-Yang Park, email: [email protected]

Keywords: multiple myeloma, IgM, IRF4, progression-free survival, sequencing

Received: October 16, 2015    Accepted: March 28, 2016    Published: May 19, 2016

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.


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