Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma

Liang Cheng, Timothy D. Jones, Ryan P. McCarthy, John N. Eble, Mingsheng Wang, Gregory T. MacLennan, Antonio Lopez-Beltran, Ximing J. Yang, Michael O. Koch, Shaobo Zhang, Chong-Xian Pan, Lee Ann Baldridge

Research output: Contribution to journalArticle

142 Scopus citations

Abstract

In most cases, small-cell carcinoma of the urinary bladder is admixed with other histological types of bladder carcinoma. To understand the pathogenetic relationship between the two tumor types, we analyzed histologically distinct tumor cell populations from the same patient for loss of heterozygosity (LOH) and X chromosome inactivation (in female patients). We examined five polymorphic microsatellite markers located on chromosome 3p25-26 (D3S3050), chromosome 9p21 (DFNA and D9S171), chromosome 9q32-33 (D9S177), and chromosome 17p13 (TP53) in 20 patients with small-cell carcinoma of the urinary bladder and concurrent urothelial carcinoma. DNA samples were prepared from formalin-fixed, paraffin-embedded tissue sections using laser-assisted microdissection. A nearly identical pattern of allelic loss was observed in the two tumor types in all cases, with an overall frequency of allelic loss of 90% (18 of 20 cases). Three patients showed different allelic loss patterns in the two tumor types at a single locus; however, the LOH patterns at the remaining loci were identical. Similarly, the same pattern of nonrandom X chromosome inactivation was present in both carcinoma components in the four cases analyzed. Concordant genetic alterations and X chromosome inactivation between small-cell carcinoma and coexisting urothelial carcinoma suggest that both tumor components originate from the same cells in the urothelium.

Original languageEnglish (US)
Pages (from-to)1533-1539
Number of pages7
JournalAmerican Journal of Pathology
Volume166
Issue number5
StatePublished - May 2005
Externally publishedYes

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

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    Cheng, L., Jones, T. D., McCarthy, R. P., Eble, J. N., Wang, M., MacLennan, G. T., Lopez-Beltran, A., Yang, X. J., Koch, M. O., Zhang, S., Pan, C-X., & Baldridge, L. A. (2005). Molecular genetic evidence for a common clonal origin of urinary bladder small cell carcinoma and coexisting urothelial carcinoma. American Journal of Pathology, 166(5), 1533-1539.