BRAF/KRAS and PIK3CA mutation characteristics and clinical significance in primary small cell lung caner
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 (Tang HR,Hu X,Xu YJ,Dong BQ,Wang J,Kong Y,Ma HL,Zhang XQ,Chen M),Department of Pathology (Yang SF),Zhejiang Cancer Research Institute (Xu Q),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 (Zhang JJ)
Abstract: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.
. BRAF/KRAS and PIK3CA mutation characteristics and clinical significance in primary small cell lung caner[J]. Chinese Journal of Radiation Oncology, 2018, 27(9): 805-808.