title: BRCA1, LMO4, and CtIP mRNA expression in erlotinib-treated non-small-cell lung cancer patients with EGFR mutations.
abstract: BACKGROUND
  Lung adenocarcinoma patients harboring EGFR activating mutations attain improved progression-free survival (PFS) with treatment with epidermal growth factor receptor tyrosine kinase inhibitors. However, patients ultimately relapse, indicating that other genetic factors could influence outcome in such patients. We hypothesized that PFS could be influenced by the expression of genes in DNA repair pathways.
  
  
  METHODS
  We examined the mRNA expression of C terminus-binding protein-interacting protein and Lin11, Isl-1, and Mec-3 domain only 4 (LMO4) in pretreatment tumor samples from 91 erlotinib-treated advanced non-small-cell lung cancer patients with EGFR mutations in whom breast cancer gene 1 (BRCA1) expression and the concomitant presence of the EGFR T790M mutation had previously been assessed. Gene expression was analyzed by polymerase chain reaction, using β-actin as endogenous gene. Results were correlated with PFS and overall survival.
  
  
  RESULTS
  In patients with low LMO4 levels, PFS was 13 months, whereas it was not reached for those with high LMO4 levels (p = 0.03). In patients with low levels of both BRCA1 and LMO4, PFS was 19 months whereas it was not reached in those with low BRCA1 and high LMO4 mRNA levels (p = 0.04). In patients with high BRCA1 and low LMO4 levels, PFS was 8 months, whereas it was 18 months in those with high levels of both genes (p = 0.03).
  
  
  CONCLUSIONS
  Low BRCA1 and high LMO4 levels were associated with longer PFS to erlotinib. Baseline assessment of BRCA1 and LMO4 mRNA expression can help predict outcome to erlotinib.
authors: Pangaea Biotech, Dexeus University Institute, Barcelona, Spain.
authors: Niki
authors: N
authors: Karachaliou
authors: Carlota
authors: C
authors: Costa
authors: Ana
authors: A
authors: Gimenez-Capitan
authors: Miguel Angel
authors: MA
authors: Molina-Vila
authors: Jordi
authors: J
authors: Bertran-Alamillo
authors: Clara
authors: C
authors: Mayo
authors: Bartomeu
authors: B
authors: Massuti
authors: Margarita
authors: M
authors: Majem
authors: Enric
authors: E
authors: Carcereny
authors: Teresa
authors: T
authors: Moran
authors: Jose Javier
authors: JJ
authors: Sanchez
authors: Santiago
authors: S
authors: Viteri
authors: Amaya
authors: A
authors: Gasco
authors: Luciano
authors: L
authors: Wannesson
authors: John
authors: J
authors: Souglakos
authors: Jose
authors: J
authors: Jimeno
authors: Rafael
authors: R
authors: Rosell
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics*; D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D002282:Adenocarcinoma, Bronchiolo-Alveolar / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D019313:BRCA1 Protein / Q000235:genetics*; D014408:Biomarkers, Tumor / Q000235:genetics; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000401:mortality; D002352:Carrier Proteins / Q000235:genetics*; D004706:Endodeoxyribonucleases; D066246:ErbB Receptors / Q000235:genetics*; D000069347:Erlotinib Hydrochloride; D005260:Female; D005500:Follow-Up Studies; D020869:Gene Expression Profiling; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics*; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D009687:Nuclear Proteins / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D011379:Prognosis; D011446:Prospective Studies; D047428:Protein Kinase Inhibitors / Q000627:therapeutic use; D011799:Quinazolines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics*; D060888:Real-Time Polymerase Chain Reaction; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D055815:Young Adult
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D019313:BRCA1 Protein; C492913:BRCA1 protein, human; D014408:Biomarkers, Tumor; D002352:Carrier Proteins; D060588:LIM Domain Proteins; C114905:LMO4 protein, human; D009687:Nuclear Proteins; D047428:Protein Kinase Inhibitors; D011799:Quinazolines; D012333:RNA, Messenger; D000069347:Erlotinib Hydrochloride; C512478:EGFR protein, human; D066246:ErbB Receptors; D004706:Endodeoxyribonucleases; C410741:RBBP8 protein, human