title: VHL tumor suppressor gene: its mutation and protein level in renal cell carcinoma.
abstract: In this study, we identified mutations in the von Hippel-Lindau gene (VHL) in patients with sporadic clear cell renal carcinoma and analyzed the relationship between these VHL mutations and VHL protein (pVHL) expression levels. Analysis of VHL coding region mutations by direct polymerase chain reaction in 39 patients with clear cell renal carcinoma, who had all undergone radical nephrectomy, revealed heterozygous mutations in 7 (17.9%) of the 39 patients, including 2 novel mutations. Analysis of the levels of pVHL expression in tumor tissue samples from the 7 patients with mutations by Western blot analysis demonstrated that pVHL was not expressed in 3 patients, and that 3 subjects expressed about 50%, and 1 was similar to the normal level. These results suggest that the 3 patients who did not express pVHL had both mutation and loss of heterozygosity, and that the 3 patients who expressed about 50% of the normal pVHL level had heterozygous mutations.
authors.affiliation: Department of Urology, St. Marianna University School of Medicine, Kawasaki 216-8511, Japan.
authors.forename: Hisashi
authors.initials: H
authors.lastname: Tsutsumi
authors.forename: Chikara
authors.initials: C
authors.lastname: Miyamoto
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Furuichi
authors.forename: Miki
authors.initials: M
authors.lastname: Yoshiike
authors.forename: Shiari
authors.initials: S
authors.lastname: Nozawa
authors.forename: Teruaki
authors.initials: T
authors.lastname: Iwamoto
mesh_terms: D000595:Amino Acid Sequence; D015153:Blotting, Western; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism*; D004247:DNA / Q000737:chemistry; D004252:DNA Mutational Analysis; D005091:Exons; D006579:Heterozygote; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism*; D019656:Loss of Heterozygosity; D008957:Models, Genetic; D008969:Molecular Sequence Data; D009154:Mutation; D025521:Tumor Suppressor Proteins / Q000096:biosynthesis* / Q000235:genetics*; D044767:Ubiquitin-Protein Ligases / Q000096:biosynthesis* / Q000235:genetics*; D051794:Von Hippel-Lindau Tumor Suppressor Protein
chemical_list: D025521:Tumor Suppressor Proteins; D004247:DNA; D044767:Ubiquitin-Protein Ligases; D051794:Von Hippel-Lindau Tumor Suppressor Protein; C497446:VHL protein, human