Structure and Methylation-Based Silencing of a Gene (DBCCR1) within a Candidate Bladder Cancer Tumor Suppressor Region at 9q32–q33

Habuchi, Tomonori; Luscombe, Mike; Elder, Patricia A.; Knowles, Margaret A.

doi:10.1006/geno.1997.5165

Cited by 118 publications

(62 citation statements)

References 35 publications

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“…Apparent monosomy was rare and a relatively high number of tumours with interstitial deletions was observed. This allowed us to identify five putative TSG loci: two were newly described, 9q22 and 9q31; the three others, 9p21, 9q33 and 9q34, have been reported in other studies, and putative TSGs in these regions have been proposed (Cairns et al, 1994;Tanaka et al, 1995;Habuchi et al, 1998;Hornigold et al, 1999). Evidence for the implication of the 9q22 region in UC was also suggested.…”

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confidence: 74%

Alteration of the PATCHED locus in superficial bladder cancer

et al. 2003

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Chromosome 9 alterations are the most frequently encountered cytologic anomalies in urothelial carcinoma (UC). We previously screened 139 low-stage UCs for loss of heterozygosity on chromosome 9, and identified five distinct regions likely to harbour tumour-suppressor genes. The present study focused on deletion mapping in the 9q22 region with 11 additional microsatellite markers. New deletions in the 9q22 region were found in five tumours. Deletion mapping allowed us to identify a 0.5 CM common minimal region of deletion between markers D9S280 and D9S1809, encompassing PATCHED (PTC), a gene identified as a tumour suppressor in basal cell carcinoma and in medulloblastoma. A marker located in the first intron of this gene showed the highest percentage of deletion (45%). cDNA sequencing in 15 tumours with deletion of PTC showed no mutation in the remaining allele. However, average expression of PTC mRNA measured by semiquantitative RT-PCR was significantly decreased in tumours with LOH in the 9q22 region, compared to normal urothelium (P ¼ 0.04), while it showed marked fluctuations in tumours without deletion. Our results suggest that the PTC gene is a putative suppressor at the 9q22 locus and that haploinsufficiency of this gene may be an early event in the development of papillary bladder tumours.

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confidence: 74%

Alteration of the PATCHED locus in superficial bladder cancer

et al. 2003

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“…The region includes two bladder cancer-associated genes, DBC1 mapped at 9q32-q33 (Habuchi et al, 1998;Nishiyama et al, 1999) and TSC1 mapped at 9q34 (Sampson et al, 1995). Other genes in this vicinity include PBX3, mapped at 9q33-q34 (Qin et al, 2004), ENG, which is a component of the TGF-b receptor complex and can regulate the biological effect of TGF-b in tumor angiogenesis (Parker et al, 2003) mapped at 9q33-q34.1, and the myeloid leukemia-associated gene, SET, which is a regulator of G 2 /M transition mapped at 9q34.…”

Section: Discussionmentioning

confidence: 99%

Tumor suppressive role of a 2.4 Mb 9q33–q34 critical region and DEC1 in esophageal squamous cell carcinoma

Yang

Leung

et al. 2004

Oncogene

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The key genes involved in the development of esophageal squamous cell carcinoma (ESCC) remain to be elucidated. Previous studies indicate extensive genomic alterations occur on chromosome 9 in ESCC. Using a monochromosome transfer approach, this study provides functional evidence and narrows down the critical region (CR) responsible for chromosome 9 tumor suppressing activity to a 2.4 Mb region mapping to 9q33-q34 between markers D9S1798 and D9S61. Interestingly, a high prevalence of allelic loss in this CR is also observed in primary ESCC tumors by microsatellite typing. Allelic loss is found in 30/ 34 (88%) tumors and the loss of heterozygosity (LOH) frequency ranges from 67 to 86%. Absent to low expression of a 9q32 candidate tumor suppressor gene (TSG), DEC1 (deleted in esophageal cancer 1), is detected in four Asian ESCC cell lines. Stably expressing DEC1 transfectants provide functional evidence for inhibition of tumor growth in nude mice and DEC1 expression is decreased in tumor segregants arising after long-term selection in vivo. There is 74% LOH in the DEC1 region of ESCC primary tumors. This study provides the first functional evidence for the presence of critical tumor suppressive regions on 9q33-q34. DEC1 is a candidate TSG that may be involved in ESCC development.

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“…The putative tumour suppressor gene in this region has been designated DBC1 (deleted in bladder cancer 1). Using YAC and PAC contigs spanning the DBC1 region, we identi®ed a candidate tumour suppressor gene, DBCCR1 (deleted in bladder cancer chromosomal region candidate 1) (Habuchi et al, 1998;Nishiyama et al, 1999a). DBCCR1 encodes a putative protein of 761 amino acids with a predicted mass of 88.7 kDa.…”

Section: Introductionmentioning

confidence: 99%

Negative regulation of G1/S transition by the candidate bladder tumour suppressor gene DBCCR1

et al. 2001

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Deletion of all or part of chromosome 9q is the most common genetic alteration in all stages and grades of bladder cancer. DBCCR1 (deleted in bladder cancer chromosome region candidate 1) maps to the chromosome region 9q32-33, a candidate tumour suppressor locus for bladder cancer. Although no mutations of DBCCR1 have been detected in bladder tumours, expression of DBCCR1 is silenced by promoter hypermethylation in 50% of bladder cancer cell lines analysed. Here we sought to provide functional evidence to authenticate DBCCR1 as a tumour suppressor using gene-transfer methods. Exogenous expression of DBCCR1 protein or an HA epitopetagged fusion protein, HA-DBCCR1 in NIH3T3 cells and human bladder tumour cell lines resulted in suppression of proliferation. Cell cycle analyses in NIH3T3 cells revealed that DBCCR1-mediated growth inhibition was due to an increase in the number of cells in the G 1 phase of the cell cycle. The levels of apoptosis were not altered. These results demonstrate a role for DBCCR1 in cell cycle control, thereby supporting the hypothesis that this is the tumour suppressor gene targeted by 9q32-33 deletion in bladder cancer. Oncogene (2001) 20, 2956 ± 2964.

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Structure and Methylation-Based Silencing of a Gene (DBCCR1) within a Candidate Bladder Cancer Tumor Suppressor Region at 9q32–q33

Cited by 118 publications

References 35 publications

Alteration of the PATCHED locus in superficial bladder cancer

Alteration of the PATCHED locus in superficial bladder cancer

Tumor suppressive role of a 2.4 Mb 9q33–q34 critical region and DEC1 in esophageal squamous cell carcinoma

Negative regulation of G1/S transition by the candidate bladder tumour suppressor gene DBCCR1

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