Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0005684 (bladder cancer)
 16,431 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Genomic deletions of the short arm of chromosome 8 are common in many human cancers and are frequently associated with a more aggressive tumour phenotype. One of the regions of loss of heterozygosity (LOH) on 8p22 identified in bladder cancer contains two genes, LZTS1 (FEZ1) and DBC2 (RHOBTB2) that have been shown to be mutated at low frequency in other cancers. We screened a panel of bladder tumours and bladder tumour-derived cell lines for mutations in these genes. Forty two percent of the tumours were found to have LOH in the 8p22 region and many of the cell lines have known loss of 8p. Several known polymorphisms and novel polymorphisms were detected. One possible mutation of LZTS1 (G374S) was found in a cell line. The functional significance of this is unknown but the novel serine residue created may represent a novel phosphorylation site. In DBC2, we found a single somatic mutation in a tumour (E349D) that lies in a highly conserved region of the protein. mRNA levels for both genes were reduced in the majority of bladder cancer cell lines. We conclude that neither LZTS1 nor DBC2 is commonly mutated in bladder cancer. However, neither can yet be excluded as the target of 8p22 LOH. The finding of a somatic mutation of DBC2 in a tumour sample and the down-regulation of both gene transcripts in bladder tumour cell lines may indicate that an alternative mechanism of inactivation of the second allele, for example promoter hypermethylation, is more common than mutation and this must now be examined.
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PMID:Mutation analysis of the 8p candidate tumour suppressor genes DBC2 (RHOBTB2) and LZTS1 in bladder cancer. 1592 64

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.
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PMID:DBC2 gene is silenced by promoter methylation in bladder cancer. 1864 Aug 57