title: Coexistence of EGFR with KRAS, or BRAF, or PIK3CA somatic mutations in lung cancer: a comprehensive mutation profiling from 5125 Chinese cohorts.
abstract: 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.
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: S
authors.initials: S
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: L
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Thoracic Surgery, Air Force General Hospital of PLA, Beijing 100036, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: C
authors.initials: C
authors.lastname: Huang
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Qin
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: H
authors.initials: H
authors.lastname: Liu
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: L
authors.initials: L
authors.lastname: Ren-Heidenreich
authors.affiliation: Department of Thoracic Surgery, China-Japan Friendship Hospital, Beijing 100029, China.
authors.forename: B
authors.initials: B
authors.lastname: Shi
authors.affiliation: Department of Thoracic Surgery, General Hospital of Armed Police Forces, Beijing 100039, China.
authors.forename: H
authors.initials: H
authors.lastname: Ren
authors.affiliation: Department of Thoracic Surgery, Chinese PLA General Hospital, Beijing 100853, China.
authors.forename: X
authors.initials: X
authors.lastname: Chu
authors.affiliation: China Navy General Hospital, Beijing 100037, China.
authors.forename: J
authors.initials: J
authors.lastname: Kang
authors.affiliation: China Navy General Hospital, Beijing 100037, China.
authors.forename: W
authors.initials: W
authors.lastname: Wang
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: J
authors.initials: J
authors.lastname: Xu
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: K
authors.initials: K
authors.lastname: Tang
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: H
authors.initials: H
authors.lastname: Yang
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: Y
authors.initials: Y
authors.lastname: Zheng
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: J
authors.initials: J
authors.lastname: He
authors.affiliation: SurExam Bio-Tech Co., Guangzhou 510663, China.
authors.forename: G
authors.initials: G
authors.lastname: Yu
authors.affiliation: Department of Thoracic Surgery, Peking Union Medical College Hospital, Beijing 100730, China.
authors.forename: N
authors.initials: N
authors.lastname: Liang
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002675:Child, Preschool; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases; D015331:Cohort Studies; D004252:DNA Mutational Analysis; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D015994:Incidence; D016015:Logistic Models; D008175:Lung Neoplasms / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020125:Mutation, Missense; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics*; D016283:Proto-Oncogene Proteins p21(ras); D055815:Young Adult; D018631:ras Proteins / Q000235:genetics*
chemical_list: C117307:KRAS protein, human; D011518:Proto-Oncogene Proteins; D019869:Phosphatidylinositol 3-Kinases; D058534:Class I Phosphatidylinositol 3-Kinases; C484760:PIK3CA protein, human; C512478:EGFR protein, human; D066246:ErbB Receptors; C482119:BRAF protein, human; D048493:Proto-Oncogene Proteins B-raf; D016283:Proto-Oncogene Proteins p21(ras); D018631:ras Proteins
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