%0 Journal Article %A TAKASHI KASAHARA %A VLADIMIR BILIM %A NOBORU HARA %A KOTA TAKAHASHI %A YOSHIHIKO TOMITA %T Homozygous Deletions of the INK4a/ARF Locus in Renal Cell Cancer %D 2006 %J Anticancer Research %P 4299-4305 %V 26 %N 6B %X Background: Genetic alterations of p14ARF contribute to dysfunction of p53 pathways by disruption of MDM2-mediated inhibition of p53. P14ARF was investigated by focusing on the homozygous deletion (HD) in the INK4a/ARF locus and hypermethylation of the p14ARF promoter in renal cell cancer (RCC). Materials and Methods: Using 6 RCC cell lines, RT-PCR and Western blotting was performed for p14ARF. 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 p14ARF 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. Copyright© 2006 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved %U https://ar.iiarjournals.org/content/anticanres/26/6B/4299.full.pdf