Aberrations of the p14(ARF) and p16(INK4a) genes in renal cell carcinomas.
The INK4a / ARF locus on chromosome 9p21, which encodes two distinct genes, p14(ARF) and p16(INK4a), is frequently altered in human neoplasms. To investigate the potential roles of p14(ARF) and p16(INK4a) 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 p14(ARF) and p16(INK4a) gene products using differential PCR, methylation-specific PCR, and immunohistochemistry, respectively. Five cell lines showed homozygous co-deletion of both genes and one demonstrated promoter hypermethylation of the p16(INK4a) gene only. Eight of 91 RCCs showed aberrations of p14(ARF) or p16(INK4a) status and six of these featured gross extension into the renal vein. The results suggest that p14(ARF) and p16(INK4a) aberrations may play roles in the relatively late stage of renal tumorigenesis associated with tumor progression.
Kawada
Y
Y
Second Department of Pathology, Nara Medical University, Kashihara, Nara 634-8521, Japan. nkonishi@naramed-u.ac.jp
Nakamura
M
M
Ishida
E
E
Shimada
K
K
Oosterwijk
E
E
Uemura
H
H
Hirao
Y
Y
Chul
K S
KS
Konishi
N
N
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology; D002899:Chromosomes, Human, Pair 9 / Q000235:genetics; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics* / Q000378:metabolism; D004252:DNA Mutational Analysis; D006801:Humans; D007150:Immunohistochemistry; D009154:Mutation / Q000235:genetics*; D016133:Polymerase Chain Reaction; D014407:Tumor Cells, Cultured; D025803:Tumor Suppressor Protein p14ARF / Q000235:genetics* / Q000378:metabolism
D019941:Cyclin-Dependent Kinase Inhibitor p16; D025803:Tumor Suppressor Protein p14ARF