title: The presence of HER2 exon 20 insertion in patients with central nervous system metastases from non-small lung cancer--a potential application in classification for therapy.
abstract: BACKGROUND
  HER2 (ErbB2/neu) is a member of the ErbB family of four structurally related receptors of tyrosine kinase activity. Overexpression of ErbB-1 (EGFR) and HER2 is found in many human cancers, but the presence of these genes mutations determines the effectiveness of EGFR and HER2 tyrosine kinase inhibitors in the therapy of non-small cell lung cancer (NSCLC).
  
  
  METHODS
  To search for insertions of the HER2 gene in exon 20 in 150 brain metastases of non-small cell lung cancer patients, we used a PCR technique based on analysis of amplified DNA fragment lengths. We also compared the HER2 mutational status with clinicopathologic features and the presence of EGFR and BRAF mutations.
  
  
  RESULTS
  HER2 mutation was present in one male, non-smoking patient with low differentiated adenocarcinoma (0.67% of all patients and 1.5% of patients with adenocarcinoma). The mutations of EGFR and BRAF genes were not found in HER2-mutated patient.
  
  
  CONCLUSIONS
  The literature data suggests that patients with HER2 mutations may be sensitive to tyrosine kinase inhibitors of both EGFR and HER2 receptors (e.g. afatinib). Therefore, the identification of new driver mutations in NSCLC can improve the quality of patient care by enabling the use of correct molecularly targeted therapies.
authors.affiliation: Department and Clinic of Pneumonology, Oncology and Allergology, Medical University of Lublin, ul. Jaczewskiego 8, Lublin. krapa@poczta.onet.pl
authors.forename: Marcin
authors.initials: M
authors.lastname: Nicoś
authors.forename: Paweł
authors.initials: P
authors.lastname: Krawczyk
authors.forename: Radosław
authors.initials: R
authors.lastname: Mlak
authors.forename: Marek
authors.initials: M
authors.lastname: Sawicki
authors.forename: Bożena
authors.initials: B
authors.lastname: Jarosz
authors.forename: Tomasz
authors.initials: T
authors.lastname: Powrózek
authors.forename: Piotr
authors.initials: P
authors.lastname: Milanowski
authors.forename: Tomasz
authors.initials: T
authors.lastname: Trojanowski
authors.forename: Janusz
authors.initials: J
authors.lastname: Milanowski
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001932:Brain Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics* / Q000556:secondary*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000556:secondary; D066246:ErbB Receptors / Q000235:genetics; D005091:Exons / Q000235:genetics; D005260:Female; D015870:Gene Expression; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D058990:Molecular Targeted Therapy / Q000379:methods; D016254:Mutagenesis, Insertional; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors; D048493:Proto-Oncogene Proteins B-raf / Q000235:genetics; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000235:genetics*; D012189:Retrospective Studies
chemical_list: D066246:ErbB Receptors; D011505:Protein-Tyrosine Kinases; D048493:Proto-Oncogene Proteins B-raf; D018719:Erb-b2 Receptor Tyrosine Kinases; C512478:EGFR protein, human; C482119:BRAF protein, human