原发小细胞肺癌中BRAF/KRAS以及PIK3CA突变的基因特征及临床特征  

BRAF/KRAS and PIK3CA mutation characteristics and clinical significance in primary small cell lung caner

作　　者：唐华容[1] 杨世峰[2] 胡晓[1] 徐裕金[1] 董百强[1] 王谨[1] 孔月[1] 马红莲[1] 张小倩[1] 许强[3] 张建军 陈明[1] Tang Huarong;Yang Shifeng;Hu Xiao;Xu Yujin;Dong Baiqiang;Wang Jin;Kong Yue;Ma Honglian;Zhang Xiaoqian;Xu Qiang;Zhang Jianjun;Chen Ming(Zhejiang Key Laboratory of Radiation Oncology,1.Department of Pathology;Zhejiang Cancer Research Institute,Zhejiang Cancer Hospital,Hangzhou 310022,China;Department of Thoracic/Head and Neck Medical Oncology,Division of Cancer Medicine,University of Texas M.D.Anderson Cancer Center,Houston,TX,7703,USA)

机构地区：[1]浙江省肿瘤医院放疗科浙江省放射肿瘤学重点实验室, 杭州310022 [2]浙江省肿瘤医院病理科浙江省放射肿瘤学重点实验室, 杭州310022 [3]浙江省肿瘤医院肿瘤研究所, 杭州310022 [4]MDAnderson 胸部/ 头颈肿瘤内科,德克萨斯州休士顿77030

出　　处：《中华放射肿瘤学杂志》2018年第9期805-809,共5页Chinese Journal of Radiation Oncology

基　　金：国家自然科学基金项目（81401911、81672972、81402540）;浙江省博士后科研项目择优资助项目（BSH1402064）

摘　　要：目的 在中国人群小细胞肺癌（SCLC）标本中检测BRAF/KRAS以及PIK3CA基因突变频率,分析这些基因突变的基因特征和临床特征.方法 2009-2014年共收集557例单纯SCLC患者组织样本.利用双脱氧测序法进行BRAF、KRAS、PIK3CA、NRAS、MEK1基因突变检测.χ2检验分析临床因素与基因突变的相关性,Kaplan-Meier法生存分析,Cox模型多因素预后分析.结果 在557例标本中检测到13例BRAF突变,突变类型包括V600E（n=5）、V600A（n=2）、V600M（n=1）、D594G（n=1）、G464E（n=1）、K601R（n=2）、S605N（n=1）.6例KRAS突变,突变类型包括G12C（n=3）、G12A（n=1）、G12D（n=1）、G13D（n=1）.4例PIK3CA突变,突变类型包括E545G（n=2）、H1047R（n=2）.另外1例NRAS突变（Q61R）和1例MEK1突变（D61Y）.这些突变基因与患者年龄、性别、吸烟状态、临床分期均无相关性.单因素生存分析结果显示基因突变组患者的生存时间比无此类突变者生存时间差,中位生存时间分别为（10.30±0.75）个月（95％CI为8.83～11.77个月）和（12.80±0.54）个月（95％CI为11.74～13.86）（P=0.011）.结论 在单纯SCLC中存在小比例的BRAF/KRAS、PIK3CA基因突变群体,这些基因突变与患者的临床特征无明显统计学相关性,但单因素生存分析显示与患者生存预后呈负相关。Objective To detect the frequency of BRAF/ KRAS and PIK3CA mutations in the small cell lung cancer （SCLC） specimens from a large population of Chinese patients and to analyze the gene mutation and clinical characteristics. Methods A total of 557 samples were collected from SCLC patients from 2009 to 2014.BRAF,KRAS,PIK3CA,NRAS and MEK1 gene mutations were detected by the dideoxy sequencing. Chi-square test was adopted to analyze the correlation between clinical factors and gene mutation. Kaplan-Meier method was utilized for survival analysis. Cox model was used for multivariate prognostic analysis. Results BRAF mutations were detected in 13 out of 557 specimens. The mutation types included V600E （n= 5） ,V600A （n= 2） ,V600M （n= 1） ,D594G （n= 1）,G464E （n= 1）,K601R （n= 2） and S605N （n= 1）.KRAS mutation was detected in 6 cases including G12C （n= 3）,G12A （n= 1）,G12D （n=1） andG13D （n= 1）.PIK3CA mutation was observed in 4 samples including E545G （n= 2） and H1047R （n= 2）.Besides,NRAS mutation （Q61R） was detected in 1 case and MEK1 mutation （D61Y） was noted in 1 case. These gene mutations were not significantly correlated with the age, gender, smoking status and clinical staging of the patients. Univariate survival analysis demonstrated the median survival time of patients with gene mutation was （10.30±0. 751） months （95%CI：8. 829-11. 771 months）,significantly shorter than （12.80±0. 543） months （95%CI：11. 736-13. 864 months） of their counterparts without gene mutation （P=0. 011）. Conclusions BRAF/ KRAS and PIK3CA gene mutation is detected in a small proportion of SCLC patients. These gene mutations are not significantly correlated with the clinical characteristics. Univariate survival analysis demonstrates that negative these gene mutations are negatively correlated with the clinical prognosis of SCLC patients.

关 键 词：小细胞肺癌 BRAF基因 KRAS基因 PIK3CA基因 基因突变 

分 类 号：R734.2[医药卫生—肿瘤]