Oncotarget

Research Papers:

Recurrent mutations of MAPK pathway genes in multiple myeloma but not in amyloid light-chain amyloidosis

Seok Jin Kim, Hyun-Tae Shin, Hae-Ock Lee, Nayoung K.D. Kim, Jae Won Yun, Jee Hyang Hwang, Kihyun Kim, Woong-Yang Park _

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Oncotarget. 2016; 7:68350-68359. https://doi.org/10.18632/oncotarget.12029

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Abstract

Seok Jin Kim1,*, Hyun-Tae Shin2,*, Hae-Ock Lee2,*, Nayoung K.D. Kim2, Jae Won Yun2, Jee Hyang Hwang3, Kihyun Kim1, Woong-Yang Park2

1Division of Hematology-Oncology, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea

2Samsung Genome Institute, Samsung Medical Center, Department of Molecular Cell Biology, Sungkyunkwan University School of Medicine, Seoul, Korea

3Samsung Biomedical Research Institute, Samsung Medical Center, Seoul, Korea

*Co-first authors, these authors contributed equally to this work

Correspondence to:

Kihyun Kim, email: kihyun.kim@samsung.com

Woong-Yang Park, email: woongyang.park@samsung.com

Keywords: multiple myeloma, cancer panel, MAPK pathway, amyloidosis

Received: March 31, 2016     Accepted: August 10, 2016     Published: September 15, 2016

ABSTRACT

Clinically applicable platforms revealing actionable genomic alterations may improve the treatment efficacy of myeloma patients. In this pilot study, we used a high depth targeted sequencing panel containing 83 anti-cancer drug target genes to sequence genomic DNAs extracted from bone marrow aspirates of 23 patients with myeloma and 12 patients with amyloid light-chain (AL) amyloidosis. Mutation analysis revealed NRAS as the most commonly mutated gene (30%, 7/23) in myeloma patients followed by KRAS (26%, 6/23) and BRAF (22%, 5/23). However, no significant mutations were found in the 12 patients with AL amyloidosis. Notably, 6 of the 23 myeloma patients showed multi-site and/or multi-gene mutations in NRAS, KRAS, or BRAF, indicating compound aberrations in the Mitogen activated protein kinase (MAPK) pathway. Gene panel sequencing also revealed cytogenetic abnormalities associated with prognosis in myeloma patients. In conclusion, our pilot study suggests that targeted gene sequencing may have an important prognostic value for myeloma patients for the identification of actionable genomic alterations and cytogenetic aberrations.


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