Prevalence of BRAF V600E mutation in Chinese melanoma patients: Large scale analysis of BRAF and NRAS mutations in a 432-case cohort

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• 作者：Lu Si^a ;   ; ^d ; Yan Kong^a ;   ; ^d ; Xiaowei Xu^b ; Keith T. Flaherty^c ; Xinan Sheng^a ; Chuanliang Cui^a ; Zhihong Chi^a ; Siming Li^a ; Lili Mao^a ; Jun Guo^a ;   ; ^{guoj307@126.com}
• 关键词：Melanoma ; BRAF ; NRAS ; Mutation ; Overall survival
• 刊名：European Journal of Cancer
• 出版年：2012
• 出版时间：January 2012
• 年：2012
• 卷：48
• 期：1
• 页码：94-100
• 全文大小：234 K

文摘

Background

Mutations of NRAS and BRAF have been described in Caucasian melanomas. However, the status and the clinical significance of BRAF and NRAS mutations in the Asian population have not been investigated on a large scale.

Methods

Melanoma samples (n = 432) were analysed for mutations in exons 11 and 15 of the BRAF gene, and exons 1 and 2 of the NRAS gene in genomic DNA by polymerase chain reaction (PCR) amplification and Sanger sequencing. Mutations of BRAF and NRAS genes were correlated to clinicopathologic features and prognosis of the patients.

Results

The incidence of somatic mutations within the BRAF and NRAS genes was 25.5 % (110/432) and 7.2 % (31/432), respectively. Among the 110 patients with BRAF mutations, 98 patients (89.1 % ) had V600E mutations. Melanomas without chronic sun-induced damage (Non-CSD) were more likely (P < 0.01) to show BRAF mutations while NRAS mutation frequency was unbiased between melanoma subtypes. Patients with genetic mutations in BRAF (P < 0.01) or NRAS (P = 0.04) gene are more likely to have ulceration as compared to patients without BRAF or NRAS mutations, respectively. Both BRAF (P = 0.003) and NRAS mutations (P = 0.031) are inversely correlated to overall survival.

Conclusions

BRAF mutation is frequent while mutations in NRAS gene are rare. The most prevalent BRAF mutation type is V600E. Patients with mutations in BRAF or NRAS gene are frequently present with ulceration, and mutation in BRAF or NRAS gene is indicator for poor prognosis. Our study may warrant a clinical trial of kinase inhibitors targeting BRAF V600E in Chinese and Asian melanoma patients.