Cyclin E low molecular weight isoforms occur commonly in early-onset gastric cancer and independently predict survival.
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.
Milne
A N A
AN
Department of Pathology, University Medical Centre, Utrecht, The Netherlands. a.n.a.milne@umcutrecht.nl
Carvalho
R
R
Jansen
M
M
Kranenbarg
E K
EK
van de Velde
C J H
CJ
Morsink
F M
FM
Musler
A R
AR
Weterman
M A J
MA
Offerhaus
G J A
GJ
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
D014408:Biomarkers, Tumor; C475820:CCNE1 protein, human; D019927:Cyclin E; D015513:Oncogene Proteins; D020033:Protein Isoforms