Impact of MDM2 SNP309 genotype on progression and survival of stage 4 neuroblastoma.
Circumvention of the p53 checkpoint in neuroblastoma (NB) might arise from increased expression of its main negative regulator MDM2. The SNP309, a T-to-G substitution in the MDM2 promoter, was associated with higher levels of MDM2 mRNA and protein, with consequent attenuation of the p53 pathway. The association between MDM2 SNP309 and disease progression and survival was evaluated in a cohort of 142 children with stage 4 NB. The SNP309 GG patients had a worse overall survival and a worse survival after relapse than the TT ones, whereas the heterozygotes showed an intermediate behaviour (p=0.043 and p=0.049, respectively, log-rank test for trend). No evident association between SNP309 and event free survival was found. The lack of association between SNP309 and MYCN status indicates that MDM2 SNP309 may be a new independent prognostic factor for stage 4 NB.
Perfumo
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Molecular Mutagenesis and DNA Repair Unit, National Institute for Cancer Research, Genova, Italy. chiara.perfumo@istge.it
Parodi
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S
Mazzocco
K
K
Defferrari
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R
Inga
A
A
Haupt
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R
Fronza
G
G
Tonini
G P
GP
D002648:Child; D002889:Chromosomes, Human, Pair 2 / Q000235:genetics; D018450:Disease Progression; D018572:Disease-Free Survival; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D009447:Neuroblastoma / Q000235:genetics* / Q000401:mortality; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length / Q000235:genetics*; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics*
C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2