Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts

• Published in: British journal of cancer Vol. 110; no. 11; pp. 2812 - 2820
• Main Authors: Li, S, Li, L, Zhu, Y, Huang, C, Qin, Y, Liu, H, Ren-Heidenreich, L, Shi, B, Ren, H, Chu, X, Kang, J, Wang, W, Xu, J, Tang, K, Yang, H, Zheng, Y, He, J, Yu, G, Liang, N
• Format: Journal Article
• Language: English
• Published: London Nature Publishing Group UK 27.05.2014; Nature Publishing Group
• Subjects: 631/208/737; 692/699/67/1612/1350; 692/699/67/2324; 692/699/67/68; Adolescent; Adult; Aged; Aged, 80 and over; Biological and medical sciences; Biomedical and Life Sciences; Biomedicine; Cancer Research; Cancer therapies; Carcinoma, Non-Small-Cell Lung - epidemiology; Carcinoma, Non-Small-Cell Lung - genetics; Child; Child, Preschool; China; Class I Phosphatidylinositol 3-Kinases; Clinical significance; Cohort Studies; DNA Mutational Analysis; Drug Resistance; Epidemiology; Epidermal growth factor; Female; Gender; Histology; Humans; Incidence; Kinases; Logistic Models; Lung cancer; Lung Neoplasms - epidemiology; Lung Neoplasms - genetics; Male; Medical sciences; Middle Aged; Molecular Medicine; Multiple tumors. Solid tumors. Tumors in childhood (general aspects); Multivariate Analysis; Mutation; Mutation, Missense; Oncology; Phosphatidylinositol 3-Kinases - genetics; Pneumology; Proto-Oncogene Proteins - genetics; Proto-Oncogene Proteins B-raf - genetics; Proto-Oncogene Proteins p21(ras); ras Proteins - genetics; Receptor, Epidermal Growth Factor - genetics; Smoking; Thoracic surgery; Tumors; Tumors of the respiratory system and mediastinum; Young Adult; Asia; China; Beijing China; United States > US; non-small cell lung cancer; somatic mutations; multiplex testing; double and triple mutations; liquid chip technology; Lung cancer; non-small cell lung carcinoma; Epidermal growth factor receptor; K ras Gene; Somatic mutation; BRAF Gene; Cancerology; Technology; Cohort study; Bronchus disease; Genetics; Protooncogene; Lung disease; Enzyme; Respiratory disease; Transferases; Malignant tumor; Medical screening; 1-Phosphatidylinositol 3-kinase; C-Onc gene; Chinese; Cancer
• ISSN: 0007-0920; 1532-1827
• DOI: 10.1038/bjc.2014.210

Background: Determining the somatic mutations of epidermal growth factor receptor (EGFR)-pathway networks is the key to effective treatment for non-small cell lung cancer (NSCLC) with tyrosine kinase inhibitors (TKIs).The somatic mutation frequencies and their association with gender, smoking history and histology was analysed and reported in this study. Methods: Five thousand one hundred and twenty-five NSCLC patients’ pathology samples were collected, and EGFR , KRAS , BRAF and PIK3CA mutations were detected by multiplex testing. The mutation status of EGFR , KRAS , BRAF and PIK3CA and their association with gender, age, smoking history and histological type were evaluated by appropriate statistical analysis. Results: EGFR , KRAS , BRAF and PIK3CA mutation rates revealed 36.2%, 8.4%, 0.5% and 3.3%, respectively, across the 5125 pathology samples. For the first time, evidence of KRAS mutations were detected in two female, non-smoking patients, age 5 and 14, with NSCLC. Furthermore, we identified 153 double and coexisting mutations and 7 triple mutations. Interestingly, the second drug-resistant mutations, T790M or E545K, were found in 44 samples from patients who had never received TKI treatments. Conclusions: EGFR exons 19, 20 and 21, and BRAF mutations tend to happen in females and non-smokers, whereas KRAS mutations were more inclined to males and smokers. Activating and resistant mutations to EGFR-TKI drugs can coexist and ‘second drug-resistant mutations’, T790M or E545K, may be primary mutations in some patients. These results will help oncologists to decide candidates for mutation testing and EGFR-TKI treatment.