RT Journal Article SR Electronic T1 Homozygous Deletions of the INK4a/ARF Locus in Renal Cell Cancer JF Anticancer Research JO Anticancer Res FD International Institute of Anticancer Research SP 4299 OP 4305 VO 26 IS 6B A1 TAKASHI KASAHARA A1 VLADIMIR BILIM A1 NOBORU HARA A1 KOTA TAKAHASHI A1 YOSHIHIKO TOMITA YR 2006 UL http://ar.iiarjournals.org/content/26/6B/4299.abstract AB 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