Homozygous deletions of the INK4a/ARF locus in renal cell cancer.

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.

• Authors: Takashi Kasahara, Vladimir Bilim, Noboru Hara, Kota Takahashi, Yoshihiko Tomita
• Journal: Anticancer research (Anticancer Res) 2006 Nov-Dec Vol. 26 Issue 6B Pg. 4299-305 ISSN: 0250-7005 [Print] Greece
• PMID: 17201148 (Publication Type: Journal Article)

Chemical References

• Cyclin-Dependent Kinase Inhibitor p16
• DNA Primers

Topics

• Base Sequence
• Carcinoma, Renal Cell (genetics)
• Cyclin-Dependent Kinase Inhibitor p16 (genetics)
• DNA Methylation
• DNA Primers
• Gene Deletion
• Homozygote
• Humans
• Kidney Neoplasms (genetics)
• Reverse Transcriptase Polymerase Chain Reaction