Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts
| Autor: | L Ren-Heidenreich, N Liang, L Li, Y Qin, J He, C Huang, Shawn S.-C. Li, K Tang, Hong-Feng Liu, H Yang, J Kang, Y Zheng, H Ren, W Wang, Y Zhu, B Shi, X Chu, G Yu, J Xu |
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| Rok vydání: | 2014 |
| Předmět: |
Male
Oncology Cancer Research Lung Neoplasms Epidemiology DNA Mutational Analysis medicine.disease_cause Cohort Studies Phosphatidylinositol 3-Kinases T790M Carcinoma Non-Small-Cell Lung Missense mutation Epidermal growth factor receptor Child Aged 80 and over Mutation Incidence Middle Aged ErbB Receptors Child Preschool Female KRAS double and triple mutations Adult Proto-Oncogene Proteins B-raf China medicine.medical_specialty Adolescent Class I Phosphatidylinositol 3-Kinases Mutation Missense Biology Proto-Oncogene Proteins p21(ras) Young Adult Germline mutation Proto-Oncogene Proteins Internal medicine medicine Carcinoma Humans liquid chip technology Lung cancer neoplasms non-small cell lung cancer Aged medicine.disease respiratory tract diseases Logistic Models multiplex testing Multivariate Analysis Immunology ras Proteins biology.protein somatic mutations |
| Zdroj: | British Journal of Cancer |
| ISSN: | 1532-1827 0007-0920 |
| DOI: | 10.1038/bjc.2014.210 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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