Prevalence and Clinicopathologic Significance ofBRAF V600EMutation in Chinese Multiple Myeloma Patients

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Abstract

Background:

Previous studies in Western countries demonstrated BRAF V600E mutation only in a small subset of multiple myeloma (MM) patients. However, the prevalence and clinicopathologic significances of this mutation remain unclear in Chinese MM patients.

Patients and Methods:

We studied diagnostic bone marrow samples from 205 Chinese MM patients by allele-specific PCR to detect BRAF V600E mutation and by high-resolution melting assay to detect KRAS and NRAS mutations. The mutations were confirmed by independent assays.

Results:

BRAF V600E mutation was found in 9.3% of the cases, the highest prevalence hitherto reported. In addition, the mutation was significantly associated with hypercalcemia and a male predominance but not with aggressive extramedullary diseases or a high serum creatinine level as reported in Western studies. Importantly, BRAF V600E mutation was an adverse prognostic factor for overall survival in younger MM patients by subgroup analysis. Concurrent analysis of RAS mutations highlighted differential alteration spectrum of RAS signaling between Chinese and Western MM, which may suggest a unique myeloma-related genetic profile in Chinese patients.

Conclusion:

Our study revealed a higher prevalence of BRAF V600E mutation in Chinese MM patients. The associated prognostic impacts on younger patients could be beneficial to risk stratification and potential application of BRAF-targeted therapies in Chinese MM management. This is the first large-scale study revealing the prevalence and clinicopathologic significances of BRAF V600E mutation in Chinese myeloma.

Micro-Abstract

On the basis of the study of 205 Chinese patients with multiple myeloma, we demonstrated a prevalence of 9.3% of BRAF V600E mutation, the highest hitherto reported. Additionally, BRAF V600E mutation was found to be associated with hypercalcemia and a male predominance. In subgroup analysis, the BRAF V600E mutation showed prognostic impact on overall survival in younger patients (<65 years old). This is the first large-scale study to reveal the prevalence and clinicopathologic significance of BRAF V600E mutation in myeloma in Chinese patients.

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