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      Mdm2 Snp309 G allele displays high frequency and inverse correlation with somatic P53 mutations in hepatocellular carcinoma

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      Author
      Acun T.
      Terzioǧlu-Kara, E.
      Konu, O.
      Ozturk, M.
      Yakicier, M. C.
      Date
      2010
      Source Title
      Mutation Research - Fundamental and Molecular Mechanisms of Mutagenesis
      Print ISSN
      1386-1964
      Publisher
      Elsevier
      Volume
      684
      Issue
      1-2
      Pages
      106 - 108
      Language
      English
      Type
      Article
      Item Usage Stats
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      Abstract
      Loss of function of the p53 protein, which may occur through a range of molecular events, is critical in hepatocellular carcinoma (HCC) evolution. MDM2, an oncogene, acts as a major regulator of the p53 protein. A polymorphism in the MDM2 promoter, SNP309 (T/G), has been shown to alter protein expression and may thus play a role in carcinogenesis. MDM2 SNP309 is also associated with HCC. However, the role of SNP309 in hepatocarcinogenesis with respect to TP53 mutations is unknown. In this study, we investigated the distribution of the MDM2 SNP309 genotype and somatic TP53 (the p53 tumor suppressor gene) mutations in 99 human HCC samples from Africa, Europe, China and Japan. Samples exhibited striking geographical differences in their distribution of SNP309 genotypes. The frequency and spectrum of p53 mutations also varied geographically; TP53 mutations were frequent in Africa, where the SNP309 T/T genotype predominated but were rare in Europe and Japan, where the SNP309 G allele was present more frequently. TP53 mutations were detected in 18% (4/22) of SNP309 T/G and G/G and 82% (18/22) of SNP309 T/T genotype holders; this difference was statistically highly significant (P-value = 0.0006). Our results indicated that the presence of the SNP309 G allele is inversely associated with the presence of somatic TP53 mutations because they only coincided in 4% of HCC cases. This finding suggests that the SNP309 G allele may functionally replace p53 mutations, and in addition to known etiological factors, may be partly responsible for differential HCC prevalence. © 2009 Elsevier B.V. All rights reserved.
      Keywords
      Hepatocellular carcinoma
      MDM2 SNP309
      Polymorphism
      TP53
      guanine
      protein MDM2
      protein p53
      thymine
      Africa
      allele
      article
      China
      controlled study
      Europe
      gene frequency
      gene mutation
      genetic association
      genetic polymorphism
      genetic variability
      genotype
      human
      human cell
      Japan
      liver carcinogenesis
      liver cell carcinoma
      major clinical study
      molecular mechanics
      prevalence
      priority journal
      promoter region
      protein expression
      race difference
      single nucleotide polymorphism
      Alleles
      Carcinoma, Hepatocellular
      Gene Frequency
      Genes, p53
      Humans
      Liver Neoplasms
      Mutation
      Polymorphism, Single Nucleotide
      Proto-Oncogene Proteins c-mdm2
      Tumor Suppressor Protein p53
      Permalink
      http://hdl.handle.net/11693/22433
      Published Version (Please cite this version)
      http://dx.doi.org/10.1016/j.mrfmmm.2009.11.008
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