Blood Res.  2020 Sep;55(3):159-168. 10.5045/br.2020.2020137.

KRAS, NRAS, and BRAF mutations in plasma cell myeloma at a single Korean institute

• Kim Y
• Park SS
• Min CK
• Lee GD
• Son J
• Jo S
• Han E
• Han K
• Kim M

• KMID: 2507056
• DOI: http://doi.org/10.5045/br.2020.2020137

Abstract

Background
Plasma cell myeloma (PCM) is a genetically heterogeneous disease. The genetic spectrum of PCM has been expanded to mutations such as KRAS, NRAS, and BRAF genes in the RAS-RAF-MAPK pathway. In this study, we have evaluated the frequency of these mutations and their significance, including baseline characteristics and clinical outcomes.
Methods
We explored 50 patients who were newly diagnosed with PCM between 2009 and 2012 at a single Korean institute. Clinical and laboratory parameters were gathered through careful review of medical records. Mutation analysis was carried out using DNA from the bone marrow at the time of diagnosis. Pyrosequencing was performed to detect KRAS G12V,KRASG13D, and NRAS G61R. BRAF V600E was analyzed by allele-specific real-time PCR. Comparison of clinical and laboratory parameters was carried out according to those mutations.
Results
We identified 14 patients (28%) with activating mutations in the RAS-RAF-MAPK pathway (RAS/RAF mutations):KRAS (N=3), KRAS (N=4),BRAF (N=7), and both KRAS and BRAF (N=1). RAS/RAF mutations were more frequently observed in patients with complex karyotypes and showed poorer progression free survival (PFS). Specifically, the BRAF V600E mutation had a significantly negative impact on median PFS.
Conclusion
We first showed the frequency of RAS/RAF mutations in Korean patients with PCM. Screening of these mutations could be considered as a routine clinical test at the time of diagnosis and follow-up due to their influence on clinical outcome, as well as its potential as a therapeutic target.

Keyword

KRAS; KRAS; BRAF; Plasma cell myeloma

Figure

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  Fig. 1 Overview of the genetic abnormalities identified in 50 plasma cell myeloma patients.

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  Fig. 2 linical outcomes of patients with any KRAS, NRAS, and/or BRAF mutation [RAS/RAF(+)] or without mutations [RAS/RAF(-)] (A, B). Comparison between subgroups; BRAF V600E (+) vs. BRAF V600E (-) (C) and RAS (+) vs. RAS (-) (D).

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