Hypermethylation of tumor-suppressor gene CpG islands in small-cell carcinoma of the urinary bladder

Phillip H. Abbosh, Mingsheng Wang, John N. Eble, Antonio Lopez-Beltran, Gregory T. MacLennan, Rodolfo Montironi, Suqin Zheng, Chong-Xian Pan, Honghong Zhou, Liang Cheng

Research output: Contribution to journalArticlepeer-review

31 Scopus citations


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.

Original languageEnglish (US)
Pages (from-to)355-362
Number of pages8
JournalModern Pathology
Issue number3
StatePublished - Mar 2008


  • DNA methylation
  • Epigenetics
  • Small-cell carcinoma
  • Urinary bladder

ASJC Scopus subject areas

  • Pathology and Forensic Medicine


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