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Prognostic and Clinicopathologic Associations of BRAF Mutation in Primary Acral Lentiginous Melanoma in Korean Patients: A Preliminary Study

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초록

Background: In the majority of melanomas, the RAS/RAF/MEK/ERK signaling pathway is constitutively activated, dueto oncogenic mutations in the BRAF and NRAS genes. TheBRAF mutation has been mainly described in Caucasianmelanomas. However, there is a lack of study evaluating thestatus, and the clinical significance, of BRAF mutation in theAsian population. Objective: This study was aimed to determinethe frequency of BRAF mutation, and to evaluate thecorrelation of BRAF status with clinicopathologic featuresand outcomes, in Korean primary acral lentiginous melanoma(ALM) patients. Methods: ALM samples (n=36) wereanalyzed for the BRAF V600E mutation, by dual-primingoligonucleotide (DPO) based real-time polymerase chainreaction. The clinicopathologic features and prognosis of thepatients were analyzed with BRAF mutation status. Results:The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations were not associated withclinicopathologic features, except for the age factor. All ofthe BRAF-mutant patients survived without recurrence ormetastasis, and have a better clinical outcome than BRAFwild-type patients. Conclusion: In Korean primary ALM, alow frequency of BRAF mutation was shown; and BRAFmutation presented with a favorable prognosis. These resultsindicate that other distinctive genetic mechanisms may havemore important roles in the development and progression ofdisease. Further multicenter study with large sample size isfirmly needed, to confirm the results of our preliminarystudy.

Abstract

Background: In the majority of melanomas, the RAS/RAF/MEK/ERK signaling pathway is constitutively activated, dueto oncogenic mutations in the BRAF and NRAS genes. TheBRAF mutation has been mainly described in Caucasianmelanomas. However, there is a lack of study evaluating thestatus, and the clinical significance, of BRAF mutation in theAsian population. Objective: This study was aimed to determinethe frequency of BRAF mutation, and to evaluate thecorrelation of BRAF status with clinicopathologic featuresand outcomes, in Korean primary acral lentiginous melanoma(ALM) patients. Methods: ALM samples (n=36) wereanalyzed for the BRAF V600E mutation, by dual-primingoligonucleotide (DPO) based real-time polymerase chainreaction. The clinicopathologic features and prognosis of thepatients were analyzed with BRAF mutation status. Results:The incidence of BRAF V600E mutation was 19.4% (7/36). The BRAF V600E mutations were not associated withclinicopathologic features, except for the age factor. All ofthe BRAF-mutant patients survived without recurrence ormetastasis, and have a better clinical outcome than BRAFwild-type patients. Conclusion: In Korean primary ALM, alow frequency of BRAF mutation was shown; and BRAFmutation presented with a favorable prognosis. These resultsindicate that other distinctive genetic mechanisms may havemore important roles in the development and progression ofdisease. Further multicenter study with large sample size isfirmly needed, to confirm the results of our preliminarystudy.

참고문헌 (26)

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