title: Sensitive methods for screening of the MEK1 gene mutations in patients with central nervous system metastases of non-small cell lung cancer.
abstract: BACKGROUND
  The mitogen-activated protein kinases 1 and 2 (MEK1, MEK2) are fundamental partners in the RAS-RAF-MEK-ERK pathway that is involved in regulation of cell proliferation, differentiation and survival. Downregulation of the MEK cascades has been implicated in acquiring of the malignant phenotype in various cancers. Somatic mutations in MEK1 gene (substitutions K57N, Q56P, D67N) were described in <1 % of non-small cell lung cancer (NSCLC) and they were more commonly reported in adenocarcinoma patients with current or former smoking status.
  
  
  METHODS
  In the following study, we assessed the MEK1 gene mutations in 145 FFPE tissue samples from central nervous system (CNS) metastases of NSCLC using HRM-PCR and ASP-qPCR techniques. The studied group was heterogeneous in terms of histopathology and smoking status. The prevalence of the MEK1 gene mutation was correlated with the occurrence of mutations in KRAS, EGFR, DDR2, PIK3CA, NRAS, HER2, AKT1 and PTEN genes.
  
  
  RESULTS
  Using HRM and ASP-qPCR methods we identified one (0.7 %; 1/145) MEK1 substitution (Q56P) in CNS metastases of NSCLC. The mutation was identified in a single, 50-year-old, current smoking men with adenocarcinoma (1.25 %; 1/80 of all adenocarcinomas).
  
  
  CONCLUSIONS
  According to the current knowledge, the incidence of MEK1 gene mutation in CNS metastatic lesion of NSCLC is the first such report worldwide. The analysis of gene profile in cancer patients may extend the scope of molecularly targeted therapies used both in patients with primary and metastatic tumors of NSCLC.
authors: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lubin, Poland. marcin_nicos@interia.pl.|Postgraduate School of Molecular Medicine, Medical University of Warsaw, 02-091, Warsaw, Poland. marcin_nicos@interia.pl.
authors: M
authors: M
authors: Nicoś
authors: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lubin, Poland.
authors: P
authors: P
authors: Krawczyk
authors: Pathological Laboratory, Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, 20-954, Lubin, Poland.
authors: B
authors: B
authors: Jarosz
authors: Department of Thoracic Surgery, Medical University of Lublin, 20-954, Lubin, Poland.
authors: M
authors: M
authors: Sawicki
authors: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lubin, Poland.
authors: M
authors: M
authors: Michnar
authors: Pathological Laboratory, Department of Neurosurgery and Pediatric Neurosurgery, Medical University of Lublin, 20-954, Lubin, Poland.
authors: T
authors: T
authors: Trojanowski
authors: Department of Pneumology, Oncology and Allergology, Medical University of Lublin, Jaczewskiego 8, 20-954, Lubin, Poland.
authors: J
authors: J
authors: Milanowski
mesh_terms: D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor / Q000235:genetics*; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000473:pathology; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics* / Q000473:pathology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000473:pathology; D016543:Central Nervous System Neoplasms / Q000235:genetics* / Q000556:secondary; D004252:DNA Mutational Analysis / Q000379:methods*; D055088:Early Detection of Cancer / Q000379:methods; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics* / Q000473:pathology; D008207:Lymphatic Metastasis; D048369:MAP Kinase Kinase 1 / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D009154:Mutation / Q000235:genetics*; D009367:Neoplasm Staging; D011379:Prognosis; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D014408:Biomarkers, Tumor; D048369:MAP Kinase Kinase 1; C482125:MAP2K1 protein, human
keywords: ASP-qPCR; Central nervous system metastases; HRM-PCR; MEK1 mutations; NSCLC