title: Association of EGFR mutation or ALK rearrangement with expression of DNA repair and synthesis genes in never-smoker women with pulmonary adenocarcinoma.
abstract: BACKGROUND
  Epidermal growth factor receptor (EGFR) mutation and anaplastic lymphoma kinase (ALK) rearrangement may predict the outcome of targeted drug therapy and also are associated with the efficacy of chemotherapy in patients with nonsmall cell lung cancer (NSCLC). The authors of this report investigated the relation of EGFR mutation or ALK rearrangement status and the expression of DNA repair or synthesis genes, including excision repair cross-complementing 1 (ERCC1), ribonucleotide reductase subunit M1 (RRM1), thymidylate synthetase (TS), and breast cancer-early onset (BRCA1), as a potential explanation for these observations.
  
  
  METHODS
  In total, 104 resected lung adenocarcinomas from women who were nonsmokers were analyzed concurrently for EGFR mutations, ALK rearrangements, and mRNA expression of the ERCC1, RRM1, TS, and BRCA1 genes. EGFR mutations were detected with a proprietary detection kit, ALK rearrangements were detected by polymerase chain reaction analysis, and genetic mRNA expression was detected by real-time polymerase chain reaction analysis.
  
  
  RESULTS
  Of 104 patients, 73 (70.2%) had EGFR mutations, and 10 (9.6%) had ALK rearrangements. ERCC1 mRNA levels in patients who had EGFR mutations were 3.44 ± 1.94 × 10(-3) , which were significantly lower than the levels in patients who were positive for ALK rearrangements and in patients who were negative for both biomarkers (4.60 ± 1.95 × 10(-3) and 4.95 ± 2.33 × 10(-3) , respectively; P = .010). However, TS mRNA levels were significantly lower in patients who had EGFR mutations (1.15 ± 1.38 × 10(-3) vs 2.69 ± 3.97 × 10(-3) ; P = .006) or ALK rearrangements (1.21 ± 0.78 × 10(-3) vs 2.69 ± 3.97 × 10(-3) ; P = .020) than in patients who were negative for both biomarkers.
  
  
  CONCLUSIONS
  NSCLC specimens that harbored activating EGFR mutations were more likely to express low ERCC1 and TS mRNA levels, whereas patients with NSCLC who had ALK rearrangement were more likely to express low TS mRNA levels.
authors.affiliation: Department of Medical Oncology, Shanghai Pulmonary Hospital, Tongji University School of Medicine, Tongji University Medical School Cancer Institute, Shanghai, People's Republic of China.
authors.forename: Shengxiang
authors.initials: S
authors.lastname: Ren
authors.forename: Xiaoxia
authors.initials: X
authors.lastname: Chen
authors.forename: Peng
authors.initials: P
authors.lastname: Kuang
authors.forename: Limou
authors.initials: L
authors.lastname: Zheng
authors.forename: Chunxia
authors.initials: C
authors.lastname: Su
authors.forename: Jiayu
authors.initials: J
authors.lastname: Li
authors.forename: Bing
authors.initials: B
authors.lastname: Li
authors.forename: Yongshen
authors.initials: Y
authors.lastname: Wang
authors.forename: Lu
authors.initials: L
authors.lastname: Liu
authors.forename: Qiong
authors.initials: Q
authors.lastname: Hu
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.forename: Liang
authors.initials: L
authors.lastname: Tang
authors.forename: Xuefei
authors.initials: X
authors.lastname: Li
authors.forename: Caicun
authors.initials: C
authors.lastname: Zhou
authors.forename: Gerald
authors.initials: G
authors.lastname: Schmid-Bindert
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics*; D000328:Adult; D000368:Aged; D000077548:Anaplastic Lymphoma Kinase; D019313:BRCA1 Protein / Q000235:genetics; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics*; D004247:DNA / Q000096:biosynthesis; D004260:DNA Repair / Q000235:genetics*; D004261:DNA Replication / Q000235:genetics; D004268:DNA-Binding Proteins / Q000235:genetics; D004720:Endonucleases / Q000235:genetics; D066246:ErbB Receptors / Q000235:genetics*; D005260:Female; D015321:Gene Rearrangement; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics; D008875:Middle Aged; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics*; D012262:Ribonucleoside Diphosphate Reductase; D012907:Smoking; D013940:Thymidylate Synthase / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics
chemical_list: D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; D025521:Tumor Suppressor Proteins; D004247:DNA; C475286:RRM1 protein, human; D012262:Ribonucleoside Diphosphate Reductase; D013940:Thymidylate Synthase; C000626173:ALK protein, human; D000077548:Anaplastic Lymphoma Kinase; C512478:EGFR protein, human; D066246:ErbB Receptors; D020794:Receptor Protein-Tyrosine Kinases; C071447:ERCC1 protein, human; D004720:Endonucleases