DBC2 gene is silenced by promoter methylation in bladder cancer.
Deletions at 8p are frequent in many human cancers and represent a genetic marker associated with a more aggressive tumor phenotype. Previous mutational analysis of DBC2 (deleted in breast cancer 2), a tumor suppressor gene located in the region of loss of heterozygosity (LOH) on 8p21, failed to show a high frequency of mutation linked to low expression in bladder cancer. Promoter hypermethylation may be an alternative mechanism of inactivation of the second allele. We detected the methylation status and expression of the DBC2 gene in 75 bladder cancer samples and 57 corresponding normal tissues. Aberrant methylation and down-regulation of DBC2 were observed preferentially in tumor samples (P < 0.05), and the expression changes were associated with methylation (P < 0.05). These findings, together with the previously mutation reports, suggest that aberrant methylation in DBC2 promoter may be responsible for the expression loss of DBC2 expression in bladder cancer and this hypermethylation event could play a crucial role in the early stage of bladder tumorigenesis.
Shi
Ying
Y
Department of Urology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
Chen
Jian-Ying
JY
Yang
Jun
J
Li
Bin
B
Chen
Zhao-Hui
ZH
Xiao
Chuan-Guo
CG
D014408:Biomarkers, Tumor / Q000235:genetics*; D019175:DNA Methylation; D004252:DNA Mutational Analysis; D005260:Female; D019204:GTP-Binding Proteins / Q000235:genetics*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D006801:Humans; D008297:Male; D008875:Middle Aged; D011401:Promoter Regions, Genetic / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D025521:Tumor Suppressor Proteins / Q000235:genetics*; D001749:Urinary Bladder Neoplasms / Q000235:genetics*
D014408:Biomarkers, Tumor; C497336:RHOBTB2 protein, human; D025521:Tumor Suppressor Proteins; D019204:GTP-Binding Proteins