title: Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder.
abstract: Small-cell carcinoma of the urinary bladder (SCBC) is a rare tumor, which shows a common clonal origin with urothelial carcinoma. It bears a high metastatic potential, even when discovered in a localized state. Identifying the molecular underpinnings of this disease may elucidate useful clinical information regarding prevention, diagnosis, prognosis, treatment, and surveillance. As DNA methylation is widely recognized as having a pivotal role in the process of carcinogenesis, we analyzed the DNA methylation status of four frequently hypermethylated tumor suppressors in small-cell and transitional-cell carcinoma (TCC) arising concomitantly in 13 patients. Fourteen cases of pure TCC were also included in the analysis. We identified frequent methylation of RASSF1 and MGMT and infrequent methylation of MLH1 and DAPK1 in cases of concomitant TCC and SCBC. Similar rates of methylation were found in pure and concomitant histopathologies, with the exception of MGMT, which was much less frequently methylated in pure TCC. These findings suggest that SCBC and TCC have common origins, establish DNA methylation of some tumor suppressors as frequent occurrences in both histopathologies, and suggest that MGMT methylation may be an SCBC-specific epimutation.
authors.affiliation: Department of Pathology, Indiana University, Indianapolis, IN, USA.
authors.forename: Phillip H
authors.initials: PH
authors.lastname: Abbosh
authors.forename: Mingsheng
authors.initials: M
authors.lastname: Wang
authors.forename: John N
authors.initials: JN
authors.lastname: Eble
authors.forename: Antonio
authors.initials: A
authors.lastname: Lopez-Beltran
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Maclennan
authors.forename: Rodolfo
authors.initials: R
authors.lastname: Montironi
authors.forename: Suqin
authors.initials: S
authors.lastname: Zheng
authors.forename: Chong-Xian
authors.initials: CX
authors.lastname: Pan
authors.forename: Honghong
authors.initials: H
authors.lastname: Zhou
authors.forename: Liang
authors.initials: L
authors.lastname: Cheng
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics; D051017:Apoptosis Regulatory Proteins / Q000235:genetics; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics; D018288:Carcinoma, Small Cell / Q000235:genetics* / Q000473:pathology; D002295:Carcinoma, Transitional Cell / Q000235:genetics* / Q000473:pathology; D018899:CpG Islands / Q000235:genetics*; D019175:DNA Methylation; D015254:DNA Modification Methylases / Q000235:genetics; D045643:DNA Repair Enzymes / Q000235:genetics; D064550:Death-Associated Protein Kinases; D016147:Genes, Tumor Suppressor; D006801:Humans; D000070957:MutL Protein Homolog 1; D009687:Nuclear Proteins / Q000235:genetics; D025521:Tumor Suppressor Proteins / Q000235:genetics; D001749:Urinary Bladder Neoplasms / Q000235:genetics* / Q000473:pathology
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D051017:Apoptosis Regulatory Proteins; C501486:MLH1 protein, human; D009687:Nuclear Proteins; C411762:RASSF1 protein, human; D025521:Tumor Suppressor Proteins; D015254:DNA Modification Methylases; C515491:MGMT protein, human; C579096:DAPK1 protein, human; D064550:Death-Associated Protein Kinases; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D000070957:MutL Protein Homolog 1; D045643:DNA Repair Enzymes