title: Comparison of EGFR signaling pathway somatic DNA mutations derived from peripheral blood and corresponding tumor tissue of patients with advanced non-small-cell lung cancer using liquidchip technology.
abstract: Somatic DNA mutations affecting the epidermal growth factor receptor (EGFR) signaling pathway are known to predict responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers. We evaluated a sensitive liquidchip platform for detecting EGFR, KRAS (alias Ki-ras), proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations in plasma samples, which were highly correlated with matched tumor tissues from 86 patients with advanced non-small-cell lung cancers. Either EGFR exon 19 or 21 mutations were detected in 36 patients: 23 of whom had identical mutations in both their blood and tissue samples; whereas mutations in the remaining 13 were found only in their tumor samples. These EGFR mutations occurred at a significantly higher frequency in females, never-smokers, and in patients with adenocarcinomas (P ≤ 0.001). The EGFR exon 20 T790M mutation was detected in only one of the paired samples [100% (95% CI, 96% to 100%) agreement]. For KRAS, proto-oncogene B-Raf, and phosphatidylinositol 3-kinase CA mutations, the overall agreements were 97% (95% CI, 90% to 99%), 98% (95% CI, 92% to 99%), and 97% (95% CI, 90% to 99%), respectively, and these were not associated with age, sex, smoking history, or histopathologic type. In conclusion, mutations detected in plasma correlated strongly with mutation profiles in each respective tumor sample, suggesting that this liquidchip platform may offer a rapid and noninvasive method for predicting tumor responsiveness to EGFR-tyrosine kinase inhibitor drugs in patients with advanced non-small-cell lung cancers.
authors.affiliation: Department of Medical Oncology, Beijing Chest Hospital, Capital Medical University, Beijing, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Zhang
authors.forename: Deruo
authors.initials: D
authors.lastname: Liu
authors.forename: Shanqing
authors.initials: S
authors.lastname: Li
authors.forename: Yongqing
authors.initials: Y
authors.lastname: Zheng
authors.forename: Xinjie
authors.initials: X
authors.lastname: Yang
authors.forename: Xi
authors.initials: X
authors.lastname: Li
authors.forename: Quan
authors.initials: Q
authors.lastname: Zhang
authors.forename: Na
authors.initials: N
authors.lastname: Qin
authors.forename: Jialin
authors.initials: J
authors.lastname: Lu
authors.forename: Lifen
authors.initials: L
authors.lastname: Ren-Heidenreich
authors.forename: Huiyi
authors.initials: H
authors.lastname: Yang
authors.forename: Yuhua
authors.initials: Y
authors.lastname: Wu
authors.forename: Xinyong
authors.initials: X
authors.lastname: Zhang
authors.forename: Jingying
authors.initials: J
authors.lastname: Nong
authors.forename: Yifen
authors.initials: Y
authors.lastname: Sun
authors.forename: Shucai
authors.initials: S
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002289:Carcinoma, Non-Small-Cell Lung / Q000097:blood / Q000235:genetics* / Q000473:pathology; D004247:DNA / Q000097:blood / Q000235:genetics; D004252:DNA Mutational Analysis / Q000379:methods; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000097:blood / Q000235:genetics* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras); D012680:Sensitivity and Specificity; D015398:Signal Transduction / Q000235:genetics; D014157:Transcription Factors / Q000235:genetics; D055815:Young Adult; D018631:ras Proteins / Q000235:genetics
chemical_list: C117307:KRAS protein, human; C000715470:MAS1 protein, human; D009687:Nuclear Proteins; C503859:PI3KCA protein, human; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D014157:Transcription Factors; D004247:DNA; 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