title: 19q13-ERCC1 gene copy number increase in non--small-cell lung cancer.
abstract: BACKGROUND
  Excision repair cross complementing 1 gene expression level has potential as a prognostic and predictive marker of the efficacy of chemotherapy in NSCLC. The effect of ERCC1 gene copy number (CN) variation (CNV) on ERCC1 expression and the clinical outcome of patients with NSCLC are not known.
  
  
  METHODS
  Copy number variation of the 19q13.3 region carrying the ERCC1 gene, classified as gene amplification (GA) or high polysomy (HP), was evaluated on 235 formalin-fixed and paraffin-embedded tumors from resected NSCLC patient samples and 16 NSCLC cell lines using FISH. We analyzed the potential correlations between FISH status and ERCC1 expression, patient's outcome, and cisplatin sensitivity in the cohort or cell lines.
  
  
  RESULTS
  An increase of 19q13.3 gene CN was detected in 60 cases (25.5%) including 27 cases with GA and 33 cases with HP. A nonsignificant trend for higher ERCC1 expression in HP patients compared with GA and patients with low CNV was found (P = .06). In patients not treated with chemotherapy, FISH negative status cases had longer disease-free survival (DFS) compared with patients with 19q13-ERCC1 GA (P = .02). A 3-fold increase in IC50 of cisplatin in cell lines with high 19q13-ERCC1 CN compared with cells without CNV was shown.
  
  
  CONCLUSIONS
  ERCC1 CN increase assessed using FISH did not determine ERCC1 expression status but yields potential prognostic information on DFS in untreated patients with NSCLC. The clinical relevance of an association of 19q13-ERCC1 FISH status and chemosensitivity or prognosis in patients needs further investigation and validation.
authors.affiliation: INSERM U981, Villejuif, F-94805, France.
authors.forename: Elsa
authors.initials: E
authors.lastname: Vanhecke
authors.forename: Alexander
authors.initials: A
authors.lastname: Valent
authors.forename: Ximing
authors.initials: X
authors.lastname: Tang
authors.forename: Philippe
authors.initials: P
authors.lastname: Vielh
authors.forename: Luc
authors.initials: L
authors.lastname: Friboulet
authors.forename: Tao
authors.initials: T
authors.lastname: Tang
authors.forename: Aïcha
authors.initials: A
authors.lastname: Goubar
authors.forename: Yuanyuan
authors.initials: Y
authors.lastname: Li
authors.forename: Angélique
authors.initials: A
authors.lastname: Robin
authors.forename: Carmen
authors.initials: C
authors.lastname: Behrens
authors.forename: Frédéric
authors.initials: F
authors.lastname: Commo
authors.forename: Pierre
authors.initials: P
authors.lastname: Validire
authors.forename: Fabrice
authors.initials: F
authors.lastname: André
authors.forename: Ignacio I
authors.initials: II
authors.lastname: Wistuba
authors.forename: Jean-Charles
authors.initials: JC
authors.lastname: Soria
authors.forename: Ken A
authors.initials: KA
authors.lastname: Olaussen
mesh_terms: D000230:Adenocarcinoma / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D000970:Antineoplastic Agents / Q000627:therapeutic use; D015153:Blotting, Western; D018287:Carcinoma, Large Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy / Q000235:genetics / Q000401:mortality; D049109:Cell Proliferation; D002888:Chromosomes, Human, Pair 19 / Q000235:genetics*; D002945:Cisplatin / Q000627:therapeutic use; D056915:DNA Copy Number Variations / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics*; D004720:Endonucleases / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007124:Immunoenzyme Techniques; D017404:In Situ Hybridization, Fluorescence; D008175:Lung Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000401:mortality*; D008297:Male; D009367:Neoplasm Staging; D011379:Prognosis; D012333:RNA, Messenger / Q000235:genetics; D060888:Real-Time Polymerase Chain Reaction; D012189:Retrospective Studies; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015996:Survival Rate; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D004268:DNA-Binding Proteins; D012333:RNA, Messenger; C071447:ERCC1 protein, human; D004720:Endonucleases; D002945:Cisplatin
keywords: Amplification; Excision repair cross-complementing 1; Fluorescence in situ hybridization; High polysomy; Prognosis