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Cyclin E low molecular weight isoforms occur commonly in early-onset gastric cancer and independently predict survival
  1. A N A Milne1,2,
  2. R Carvalho3,
  3. M Jansen1,
  4. E K Kranenbarg4,
  5. C J H van de Velde4,
  6. F M Morsink1,
  7. A R Musler2,
  8. M A J Weterman5,
  9. G J A Offerhaus1,2
  1. 1
    Department of Pathology, University Medical Centre, Utrecht, The Netherlands
  2. 2
    Department of Pathology, Academic Medical Center, Amsterdam, The Netherlands
  3. 3
    MRC Holland, Amsterdam, The Netherlands
  4. 4
    Department of Surgery, Leiden University Medical Centre, Leiden, The Netherlands
  5. 5
    Department of Neurogenetics, Academic Medical Centre, Amsterdam, The Netherlands
  1. Dr Anya N A Milne, Pathology Dept H04.2.25, University Medical Centre Utrecht, Postbus 85500, 3508GA, Utrecht, The Netherlands; a.n.a.milne{at}umcutrecht.nl

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.

Aim: 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.

Conclusion: EOGCs have a unique molecular phenotype and LMW isoforms of cyclin E may independently influence survival in EOGC.

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Footnotes

  • Funding: The study was funded by the Vanderes Foundation.

  • Competing interests:None declared.

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