Sheen Yi-Shuan, Liao Yi-Hua, Liau Jau-Yu, Lin Ming-Hsien, Hsieh Yi-Chun, Jee Shiou-Hwa, Chu Chia-Yu
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan; Graduate Institute of Pathology, College of Medicine, National Taiwan University, Taipei, Taiwan.
Department of Dermatology, National Taiwan University Hospital and National Taiwan University College of Medicine, Taipei, Taiwan.
J Formos Med Assoc. 2016 Feb;115(2):121-7. doi: 10.1016/j.jfma.2015.02.001. Epub 2015 Mar 10.
BACKGROUND/PURPOSE: BRAF and NRAS mutations have been described in melanomas among Caucasians and some Asian populations. However, few large-scale studies have investigated the status and clinical significance of BRAF and NRAS mutations in a Taiwanese population.
Melanoma samples (n = 119) were analyzed for mutations in exons 11 and 15 of the BRAF gene, and in exons 1 and 2 of the NRAS gene. The samples were studied in genomic DNA, using polymerase chain reaction amplification and Sanger sequencing. Mutations of the BRAF and NRAS genes were then correlated with clinicopathological features and patients' prognosis.
The incidence of somatic mutations within the BRAF and NRAS genes was 14.3% (17/119 patients) and 10.1% (12/119 patients), respectively. Among the 17 patients with BRAF mutations, 15 (88.2%) had V600E mutations. BRAF mutation was frequently detected in younger patients (p = 0.0035), in thin melanomas (p = 0.0181), and in melanomas with less ulceration (p = 0.0089). NRAS mutation was more often seen in patients with lymph node metastasis (p = 0.0332). Both BRAF and NRAS mutations were not significantly correlated with overall survival and disease-free survival.
As BRAF and NRAS mutations are rare in Taiwan, BRAF- or NRAS-targeted therapies may be effective only for selected Taiwanese melanoma patients.
背景/目的：BRAF和NRAS突变在高加索人和部分亚洲人群的黑色素瘤中已有报道。然而，很少有大规模研究调查台湾人群中BRAF和NRAS突变的状况及临床意义。
对119例黑色素瘤样本进行BRAF基因第11和15外显子以及NRAS基因第1和2外显子的突变分析。样本采用聚合酶链反应扩增和桑格测序在基因组DNA中进行研究。然后将BRAF和NRAS基因的突变与临床病理特征及患者预后相关联。
BRAF和NRAS基因的体细胞突变发生率分别为14.3%（17/119例患者）和10.1%（12/119例患者）。在17例BRAF突变患者中，15例（88.2%）发生V600E突变。BRAF突变在年轻患者（p = 0.0035）、薄型黑色素瘤（p = 0.0181）以及溃疡较少的黑色素瘤中（p = 0.0089）更常被检测到。NRAS突变在有淋巴结转移的患者中更常见（p = 0.0332）。BRAF和NRAS突变均与总生存期和无病生存期无显著相关性。
由于BRAF和NRAS突变在台湾罕见，BRAF或NRAS靶向治疗可能仅对部分台湾黑色素瘤患者有效。
