title: Cyclin E low molecular weight isoforms occur commonly in early-onset gastric cancer and independently predict survival.
abstract: BACKGROUND
  Post-translational cleavage of full-length cyclin E from the N-terminus can produce low molecular weight (LMW) isoforms of cyclin E containing the C-terminus only.
  
  
  OBJECTIVE
  To assess their presence in early-onset gastric cancer (EOGC), stump cancers and conventional gastric cancers and ascertain how they influence survival in EOGC.
  
  
  METHODS
  The expression of full-length and LMW isoforms of cyclin E in 330 gastric cancers, including early-onset gastric cancer (EOGC), stump cancer and conventional gastric cancer (>45 years old) was compared using antibodies targeted to the N- and C-terminals.
  
  
  RESULTS
  LMW isoforms were found in 35% of EOGCs, compared to 8% of conventional gastric cancers and 4% of stump cancers; their presence was visualised in cell lines using western blot analysis. In addition, C-terminal staining was a positive predictor of survival in EOGC. In contrast, no correlation with survival was found with the N-terminal antibody which detects only full-length cyclin E.
  
  
  CONCLUSIONS
  EOGCs have a unique molecular phenotype and LMW isoforms of cyclin E may independently influence survival in EOGC.
authors.affiliation: Department of Pathology, University Medical Centre, Utrecht, The Netherlands. a.n.a.milne@umcutrecht.nl
authors.forename: A N A
authors.initials: AN
authors.lastname: Milne
authors.forename: R
authors.initials: R
authors.lastname: Carvalho
authors.forename: M
authors.initials: M
authors.lastname: Jansen
authors.forename: E K
authors.initials: EK
authors.lastname: Kranenbarg
authors.forename: C J H
authors.initials: CJ
authors.lastname: van de Velde
authors.forename: F M
authors.initials: FM
authors.lastname: Morsink
authors.forename: A R
authors.initials: AR
authors.lastname: Musler
authors.forename: M A J
authors.initials: MA
authors.lastname: Weterman
authors.forename: G J A
authors.initials: GJ
authors.lastname: Offerhaus
mesh_terms: D000328:Adult; D017668:Age of Onset; D014408:Biomarkers, Tumor / Q000032:analysis*; D015153:Blotting, Western; D016009:Chi-Square Distribution; D019927:Cyclin E / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D020869:Gene Expression Profiling; D006801:Humans; D008875:Middle Aged; D008970:Molecular Weight; D020411:Oligonucleotide Array Sequence Analysis; D015513:Oncogene Proteins / Q000032:analysis* / Q000737:chemistry / Q000235:genetics; D011379:Prognosis; D016016:Proportional Hazards Models; D020033:Protein Isoforms / Q000032:analysis; D013274:Stomach Neoplasms / Q000175:diagnosis*; D016019:Survival Analysis
chemical_list: D014408:Biomarkers, Tumor; C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D020033:Protein Isoforms