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  • Title: Homozygous deletions of the INK4a/ARF locus in renal cell cancer.
    Author: Kasahara T, Bilim V, Hara N, Takahashi K, Tomita Y.
    Journal: Anticancer Res; 2006; 26(6B):4299-305. PubMed ID: 17201148.
    Abstract:
    BACKGROUND: Genetic alterations of p14ARF contribute to dysfunction of p53 pathways by disruption of MDM2-mediated inhibition of p53. P14(ARF) was investigated by focusing on the homozygous deletion (HD) in the INK4a/ARF locus and hypermethylation of the p14(ARF) promoter in renal cell cancer (RCC). MATERIALS AND METHODS: Using 6 RCC cell lines, RT-PCR and Western blotting was performed for p14(ARF). DNA from 34 RCCs was analyzed for HD in the INK4a/ARF locus, promoter hypermethylation and p53 gene mutation. RESULTS: HD was confirmed in 4 out of 6 cell lines and in 8 out of 34 (23.5%) RCC specimens, which correlated with the presence of metastasis, high tumor grade and had a tendency to more advanced stage (I vs. II-IV). No hypermethylation of the p14(ARF) promoter or p53 mutation was detected among the RCC specimens. CONCLUSION: These results indicate that the deletion in the INK4a/ARF locus might contribute to tumor progression in RCC at least partly by functional inactivation of wild-type p53.
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