title: Concurrent oncogene mutation profile in Chinese patients with stage Ib lung adenocarcinoma.
abstract: Molecular characteristics in lung cancer are associated with carcinogenesis, response to targeted therapies, and prognosis. With concurrent oncogene mutations being reported more often, the adjustment of treatment based on the driver gene mutations would improve therapy. We proposed to investigate the distribution of concurrent oncogene mutations in stage Ib lung adenocarcinoma in a Chinese population and find out the correlation between survival outcome and the most frequently mutated genes in EGFR and KRAS in Chinese population. Simultaneously, we tried to validate the Sequenom method by real time fluoresce qualification reverse transcription polymerase chain reaction (RT-PCR) in oncogene detection. One hundred fifty-six patients who underwent complete surgical resection in our hospital between 1999 and 2007 were retrospectively investigated. Using time-of-flight mass spectrometry, 238 mutation hotspots in 19 oncogenes were examined. Genetic mutations occurred in 86 of 156 patients (55.13%). EGFR was most frequently gene contained driver mutations, with a rate of 44.23%, followed by KRAS (8.33%), PIK3CA (3.84%), KIT (3.20%), BRAF (2.56%), AKT (1.28%), MET (0.64%), NRAS (0.64%), HRAS (0.64%), and ERBB2 (0.64%). No mutations were found in the RET, PDGFRA, FGFR1, FGFR3, FLT3, ABL, CDK, or JAK2 oncogenes. Thirteen patients (8.3%) were detected in multiple gene mutations. Six patients had PIK3CA mutations in addition to mutations in EGFR and KRAS. EGFR mutations can coexist with mutations in NRAS, KIT, ERBB2, and BRAF. Only one case was found to have a KRAS mutation coexisting with the EGFR T790M mutation. Otherwise, mutations in EGFR and KRAS seem to be mutually exclusive. There is no survival benefit in favor of EGFR/KRAS mutation. Several concomitant driver gene mutations were observed in our study. None of EFGR/KRAS mutation was demonstrated as a prognostic factor. Polygenic mutation testing by time-of-flight mass spectrometry was validated by RT-PCR, which can be an alternative option to test for multiple mutations and can be widely applied to clinical practice and help to guide treatment.
authors.affiliation: From the Department of Thoracic Surgery; Sun Yat-sen University Cancer Center, Guangzhou, China (Y-SW, J-fZ, L-JZ); State Key Laboratory of Oncology in South China, Sun Yat-sen University Cancer Center, Guangzhou, China (Y-SW, LC, J-yS, L-JZ); Department of Radiation Oncology, Sun Yat-sen University Cancer Center, Guangzhou, China (LC); Department of Molecular Pathology, Sun Yat-sen University Cancer Center, Guangzhou, China (X-wZ, Z-cZ, J-yS); School of Medicine, University of Glasgow, Glasgow, UK (X-wZ); and Department of Thoracic Surgery, Shannxi Provincial People's Hospital, Xi'an, China (J-fZ).
authors.forename: Ying-Sheng
authors.initials: YS
authors.lastname: Wen
authors.forename: Ling
authors.initials: L
authors.lastname: Cai
authors.forename: Xue-Wen
authors.initials: XW
authors.lastname: Zhang
authors.forename: Jian-Fei
authors.initials: JF
authors.lastname: Zhu
authors.forename: Zi-Chen
authors.initials: ZC
authors.lastname: Zhang
authors.forename: Jian-Yong
authors.initials: JY
authors.lastname: Shao
authors.forename: Lan-Jun
authors.initials: LJ
authors.lastname: Zhang
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D002681:China; D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors / Q000235:genetics; D005260:Female; D020558:GTP Phosphohydrolases / Q000235:genetics; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008297:Male; D013058:Mass Spectrometry; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D019869:Phosphatidylinositol 3-Kinases / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000235:genetics; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D019859:Proto-Oncogene Proteins c-met / Q000235:genetics; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D018631:ras Proteins / Q000235:genetics
chemical_list: D058534:Class I Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D020558:GTP Phosphohydrolases; D008565:Membrane Proteins; D019869:Phosphatidylinositol 3-Kinases; D011518:Proto-Oncogene Proteins; D048493:Proto-Oncogene Proteins B-raf; D051057:Proto-Oncogene Proteins c-akt; D019009:Proto-Oncogene Proteins c-kit; D019859:Proto-Oncogene Proteins c-met; D016283:Proto-Oncogene Proteins p21(ras); D018719:Erb-b2 Receptor Tyrosine Kinases; D018631:ras Proteins; C117307:KRAS protein, human; C484760:PIK3CA protein, human; C512478:EGFR protein, human; C508053:ERBB2 protein, human; C491743:MET protein, human; C482119:BRAF protein, human; C579846:NRAS protein, human; C501009:HRAS protein, human