• Xue Bai, Yan Kong, Zhihong Chi, Xinan Sheng, Chuanliang Cui, Xuan Wang, Lili Mao, Bixia Tang, Siming Li, Bin Lian, Xieqiao Yan, Li Zhou, Jie Dai, Jun Guo, and Lu Si.
• The Key Laboratory of Carcinogenesis and Translational Research (Ministry of Education/Beijing), Department of Renal Cancer and Melanoma, Peking University Cancer Hospital and Institute, Beijing, China.
• Clin Cancer Res. 2017 Oct 15; 23 (20): 6120-6127.

AbstractPurpose: Ethnic differences are conspicuous in melanoma. This study is to obtain a comprehensive view of a genomic landscape and a better understanding of the correlations of gene mutation status with clinicopathologic characteristics and disease prognosis in the Asian population.Experimental Design: A total of 2,793 melanoma patient samples were retrospectively collected and analyzed for mutations in C-KIT, BRAF, NRAS, and PDGFRA coding regions and telomerase reverse transcriptase (TERT) promoter region by Sanger sequencing. Mutations were correlated to clinicopathologic features and overall survival.Results: The incidences of somatic mutations within the BRAF, NRAS, C-KIT, TERT-228, TERT-250, and PDGFRA genes were 23.7%, 10.4%, 8.0%, 5.9%, 5.5%, and 1.4%, respectively. Hotspot mutations accounted for 95.8% and 87.2% of BRAF and NRAS mutations, respectively; meanwhile, C-KIT and PDGFRA mutations showed more heterogeneity. BRAF, C-KIT, and NRAS mutations were mutually exclusive. BRAF, C-KIT, NRAS, and numbers of gene mutations of the MAPK pathway were all independent negative prognostic factors (P = 0.007, other P < 0.001, respectively). In acral melanoma, BRAF, C-KIT, and NRAS mutations were all independent prognostic factors of worse overall survival (all P < 0.001), whereas in mucosal melanoma, only C-KIT was (P = 0.006). Although correlated with BRAF mutations (P = 0.001 and P < 0.001 for C228T and C250T, respectively), TERT promoter gene mutations were not correlated with overall survival (P = 0.406 and 0.256, respectively).Conclusions: The MAPK pathway and TERT promoter gene mutations are differentially represented in the Asian population. Mutations in BRAF, C-KIT, and NRAS have prognostic values that vary by melanoma subtypes. Clinical treatment targeting these critical pathways should be aimed directly at these poor-prognosis subpopulations for maximum potential impact. Clin Cancer Res; 23(20); 6120-7. ©2017 AACR.©2017 American Association for Cancer Research.

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