title: c-Met Mutational Analysis in the Sema and Juxtamembrane Domains in Small-Cell-Lung-Cancer.
abstract: BACKGROUND
  c-Met mutations play a critical role in the development and progression of primary tumors and metastases. Activation of the HGF/SF-c-Met pathway determines a poor prognosis in non-small-cell and small-cell lung cancer (SCLC) patients. Missense mutations of c-Met have been identified in SCLC patients located in the juxtamembrane (JM) and in the Sema domain. To determine the role of the c-Met pathway in SCLC, we have investigated the presence of c-Met mutations in SCLC patients.
  
  
  METHODS
  Forty-four tumor tissue samples from SCLC patients were obtained with bronchoscopy before beginning treatment. Analysis of c-Met mutations was performed in exon 2 and exon 14.
  
  
  RESULTS
  Of the 44 patients included in this study, 23 were classified as limited disease and were treated with sequential or concurrent chemotherapy and thoracic radiotherapy. Twenty-one patients with extensive disease received chemotherapy alone, the majority with cisplatin or carboplatin plus etoposide. The median survival was 14 months (95% CI: 9.4 to 18.5 months) and the 2- and 5-year survival rates were 24% and 15%, respectively. Previously identified missense mutations E168D, R988C and T1010I in c-Met were not found in our study. However, novel mutations were identified, including T995I in the juxtamembrane domain (T995I) and a mutation which does not change amino acid in codon 178 in the Sema domain.
  
  
  CONCLUSIONS
  In SCLC patients, the presence of mutations in c-Met gene is a rare event. Other genetic alterations involved in the HGF/SF-c-Met pathway should be assessed to define the role of this signaling pathway in SCLC.
authors: Catalan Institute of Oncology, Hospital Germans Trias i Pujol, Medical Oncology Service, Ctra Canyet, s/n, 08916 Badalona, Barcelona, Spain.
authors: Itziar
authors: I
authors: de Aguirre
authors: Alejandro
authors: A
authors: Salvatierra
authors: Albert
authors: A
authors: Font
authors: Jose Luis
authors: JL
authors: Mate
authors: Maria
authors: M
authors: Perez
authors: Monica
authors: M
authors: Botia
authors: Miquel
authors: M
authors: Taron
authors: Rafael
authors: R
authors: Rosell
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