[Correlation of cyclin D1 overexpression to mutations of von hippel-lindau gene in renal clear cell carcinoma].
OBJECTIVE
The mutation of von Hippel-Lindau (VHL) tumor suppressor gene is closely related with tumorigenesis of renal clear cell carcinoma (RCCC). Cyclin D1 gene plays an important role in progression of RCCC by stimulating cell proliferation. This study was to determine the mutation of VHL gene in RCCC, and explore its correlation to overexpression of Cyclin D1.


METHODS
The specimens of RCCC and adjacent normal renal tissue from 50 patients were collected after surgery. Total RNA and genomic DNA were extracted from each sample. Variant exons in VHL gene were amplified by polymerase chain reaction (PCR) and sequenced, and DNA hypermethylation was detected by restriction analysis. Reverse transcription-PCR (RT-PCR) and Western blot were used to detect the expression of Cyclin D1.


RESULTS
Of the 50 specimens, 42 (84.0%) had various VHL gene mutations, 12 (24.0%) had more than 1 kind of gene mutation. Of the 57 cases of exon mutation of VHL gene, 17 (29.8%) were located in exon 1, 26 (45.6%) in exon 2, and 14 (24.6%) in exon 3. The expression of Cyclin D1 in the 42 cases with VHL gene mutation was increased to 2-10 (3.91+/-1.54) times that of normal controls (P<0.01). Cyclin D1 expression in the other 8 cases was normal.


CONCLUSIONS
There are variant mutations of VHL gene in RCCC, which may lead to overexpression of Cyclin D1.
Department of Pathology, Nanjing Medical University, Nanjing, Jiangsu 210029, P. R. China. renyongya611216@163.com
Yong-Ya
YY
Ren
Li-Jian
LJ
Du
Zhen-Qing
ZQ
Feng
Jing
J
Leng
D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000378:metabolism; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D005091:Exons; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D007680:Kidney Neoplasms / Q000235:genetics* / Q000378:metabolism; D009154:Mutation; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D051794:Von Hippel-Lindau Tumor Suppressor Protein / Q000235:genetics*
D012333:RNA, Messenger; D019938:Cyclin D1; D051794:Von Hippel-Lindau Tumor Suppressor Protein