|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
1
|
|
pubmed:dateCreated |
2002-3-28
|
|
pubmed:abstractText |
To delineate more precisely the somatic von Hippel-Lindau disease (VHL) gene alteration as well as to elucidate its etiologic role in renal tumorigenesis, we examined a total of 240 sporadic renal cell carcinomas (RCCs) for somatic VHL gene alterations by DNA-SSCP followed by sequencing, methylation-specific PCR assay, microsatellite LOH study, and Southern blot analysis. Intragenic mutation of the VHL gene was found exclusively in clear-cell or variant-type RCCs at a frequency of 51% (104/202). Hypermethylation of the VHL promoter region was detected in an additional 11 clear-cell RCCs. Microsatellite analysis demonstrated that LOH of the VHL locus was found in 140/155 (90%) informative clear-cell RCCs. The VHL gene therefore seems to be inactivated in a two-hit manner by intragenic mutation or hypermethylation plus allelic loss in clear-cell RCC. Genomic rearrangement of the VHL gene detected by Southern analysis was not found (0/216 cases); this is in contrast to germ lines in which Southern aberrations consisted of 7-19% of the mutations. Clinicopathologic data demonstrated that VHL mutation/LOH did not vary according to tumor progression in clear-cell RCC, including tumor diameter, stage, grading, distant metastasis, and lymph node metastasis. Interestingly, VHL mutation was significantly less frequent in RCCs occurring in younger (< or = 55 years) than that in older (> or = 56 years) patients. These data suggested that the inactivation of the VHL tumor-suppressor gene is a specific genetic change in clear-cell RCC, and that it may occur at an early or first step in the clear-cell tumorigenic pathway rather than as a late event.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
May
|
|
pubmed:issn |
1045-2257
|
|
pubmed:author |
pubmed-author:BabaMasayaM,
pubmed-author:HosakaMasahikoM,
pubmed-author:KanekoShigekiS,
pubmed-author:KawakamiSatoshiS,
pubmed-author:KishidaTakeshiT,
pubmed-author:KobayashiKazukiK,
pubmed-author:KondoKeiichiK,
pubmed-author:MiuraTakeshiT,
pubmed-author:MoriyamaMasatoshiM,
pubmed-author:NagashimaYojiY,
pubmed-author:NakaigawaNoboruN,
pubmed-author:NakataniYukioY,
pubmed-author:SakaiNaokiN,
pubmed-author:ShuinTaroT,
pubmed-author:YaoMasahiroM,
pubmed-author:YoshidaMinoruM
|
|
pubmed:copyrightInfo |
Copyright 2002 Wiley-Liss, Inc.
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
34
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
58-68
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:11921283-Adult,
pubmed-meshheading:11921283-Aged,
pubmed-meshheading:11921283-Aged, 80 and over,
pubmed-meshheading:11921283-Amino Acid Sequence,
pubmed-meshheading:11921283-Blotting, Southern,
pubmed-meshheading:11921283-Carcinoma, Renal Cell,
pubmed-meshheading:11921283-DNA, Neoplasm,
pubmed-meshheading:11921283-DNA Methylation,
pubmed-meshheading:11921283-DNA Mutational Analysis,
pubmed-meshheading:11921283-Female,
pubmed-meshheading:11921283-Gene Rearrangement,
pubmed-meshheading:11921283-Humans,
pubmed-meshheading:11921283-Kidney Neoplasms,
pubmed-meshheading:11921283-Ligases,
pubmed-meshheading:11921283-Loss of Heterozygosity,
pubmed-meshheading:11921283-Male,
pubmed-meshheading:11921283-Middle Aged,
pubmed-meshheading:11921283-Molecular Sequence Data,
pubmed-meshheading:11921283-Mutation,
pubmed-meshheading:11921283-Tumor Suppressor Proteins,
pubmed-meshheading:11921283-Ubiquitin-Protein Ligases,
pubmed-meshheading:11921283-Von Hippel-Lindau Tumor Suppressor Protein
|
|
pubmed:year |
2002
|
|
pubmed:articleTitle |
Comprehensive mutational analysis of the VHL gene in sporadic renal cell carcinoma: relationship to clinicopathological parameters.
|
|
pubmed:affiliation |
Department of Urology, Yokohama City University School of Medicine, Yokohama, Japan.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
