华南地区黑色素瘤癌基因突变谱分析

Oncogenic mutation profiles involved in melanoma in Southern China

目的:研究华南地区黑色素瘤的癌基因突变谱,为黑色素瘤分子靶向治疗策略的优化提供理论依据。方法:本研究收集中山大学肿瘤防治中心2000年3月至2009年4月黑色素瘤病理组织蜡块86例,其中肢端黑色素瘤28例、黏膜黑色素瘤28例、非慢性阳光损伤型黑色素瘤30例,采用Sequenom平台(Onco Carta Panel v1.0和Mass ARRAY体系)研究黑色素瘤癌基因的突变谱。结果:有38.4%(33/86)的黑色素瘤病灶可见基因突变,突变的基因包括:BRAF(16.3%)、NRAS(10.5%)、KIT(5.8%)、EGFR(4.7%)、HRAS(2.3%)、KRAS(2.3%)、MET(2.3%)和PIK3CA(1.2%)。其中BRAF突变型患者与野生型相比发病年龄早[(45.7±15.3)岁vs.(55.9±12.7)岁,P=0.01],NRAS突变型患者与野生型相比溃疡表现率高(88.9%vs.48.1%,P=0.049)。结论:本研究是对华南地区黑色素瘤癌基因突变谱的综合分析,有利于进一步指导华南地区黑色素瘤的个体化治疗。

Objective：To examine the oncogenic mutations involved in melanoma in Southern China and to provide a theoretical basis for the development of melanoma molecular targeted therapy strategy. Methods：The Sequenom platform （OncoCarta Panel v1.0 and MassARRAY System） was used to determine the prevalence of oncogene mutations in 28 acral melanoma samples, 28 mucosal mel-anoma samples, and 30 non-chronic sun-induced-damage （no-CSD） melanoma samples from Southern China. Results：At least one mu-tation was detected in 33 of the 86 melanomas （38.4%） with mutations observed in BRAF （16.3%）, NRAS （10.5%）, KIT （5.8%）, EGFR （4.7%）, HRAS （2.3%）, KRAS （2.3%）, MET （2.3%）, and PIK3CA （1.2%）. In BRAF, the age of patients with mutations was significantly lower than those without BRAF mutation （45.7±15.3 vs. 55.9±12.7, P=0.01）. Patients with mutations in NRAS were more likely to have ulceration compared with patients without NRAS mutations （88.9%vs. 48.1%, P=0.049）. Conclusions：This study represents a compre-hensive and concurrent analysis of the major recurrent oncogenic mutations involved in melanoma cases from Southern China areas. The data have implications for both clinical trial designs and therapeutic strategies.