Aberrations of the p14ARF and p16INK4a Genes in Renal Cell Carcinomas |
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| Authors: | Yoichi Kawada Mitsutoshi Nakamura Eiwa Ishida Keiji Shimada Egbert Oosterwijk Hirotsugu Uemura Yoshihiko Hirao Kim Sung Chul Noboru Konishi |
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| Affiliation: | Second Department of Pathology;Department of Urology, Nara Medical University, 840 Shijo-cho, Kashihara, Nara 634–8521;Nara Prefectural Hospital, 1–30-1 Hiramastu, Nara 631–0846;Department of Urology, University Hospital Nijimengen, St. Radboud, 6500HB, Nijimengen, Netherlands |
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| Abstract: | The INK4alARF locus on chromosome 9p21, which encodes two distinct genes, p14ARF and p16INK4a, is frequently altered in human neoplasms. To investigate the potential roles of p14ARF and p16IfiK4a genes in human renal cell carcinomas (RCCs), we analyzed 6 human RCC cell lines and 91 primary RCCs for homozygous deletion, promoter hypermethylation and expression of the p14ARF and p16INK4a gene products using differential PCR, methylation-specific PCR, and immunohistochemis-try, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16INK4a gene only. Eight of 91 RCCs showed aberrations of p14ARF or p16INK4a status and six of these featured gross extension into the renal vein. The results suggest that p14ARF and p16INK4a aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression. |
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| Keywords: | p14ARF p16'NK4a Methylation Homozygous deletion Renal cell carcinoma |
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