Molecular Genetic Alterations in the Laser-Capture-Microdissected Stroma Adjacent to Bladder Carcinoma

Ryan F. Paterson, Thomas M. Ulbright, Gregory T. MacLennan, Shaobo Zhang, Chong-Xian Pan, Christopher J. Sweeney, Curtiss R. Moore, Richard S. Foster, Michael O. Koch, John N. Eble, Liang Cheng

Research output: Contribution to journalArticle

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Abstract

BACKGROUND. Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X-chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene. METHODS. The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin-fixed, paraffin-processed tissues using laser-assisted microdissection and LOH was determined. RESULTS. The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25-26 (61%), and 9q32-33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome inactivation was frequent in the stromal cells (50% of informative specimens). CONCLUSIONS. The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis.

Original languageEnglish (US)
Pages (from-to)1830-1836
Number of pages7
JournalCancer
Volume98
Issue number9
DOIs
StatePublished - Nov 1 2003
Externally publishedYes

Fingerprint

Stromal Cells
Loss of Heterozygosity
Molecular Biology
Urinary Bladder
Lasers
Carcinoma
X Chromosome Inactivation
Chromosomes
Neoplasms
Microdissection
Cystectomy
Androgen Receptors
DNA Methylation
Paraffin
Microsatellite Repeats
Formaldehyde
Carcinogenesis
Muscles
DNA
Growth

Keywords

  • Carcinogenesis
  • Laser-capture microdissection
  • Neoplasms
  • Urinary bladder
  • Urothelial carcinoma

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Paterson, R. F., Ulbright, T. M., MacLennan, G. T., Zhang, S., Pan, C-X., Sweeney, C. J., ... Cheng, L. (2003). Molecular Genetic Alterations in the Laser-Capture-Microdissected Stroma Adjacent to Bladder Carcinoma. Cancer, 98(9), 1830-1836. https://doi.org/10.1002/cncr.11747

Molecular Genetic Alterations in the Laser-Capture-Microdissected Stroma Adjacent to Bladder Carcinoma. / Paterson, Ryan F.; Ulbright, Thomas M.; MacLennan, Gregory T.; Zhang, Shaobo; Pan, Chong-Xian; Sweeney, Christopher J.; Moore, Curtiss R.; Foster, Richard S.; Koch, Michael O.; Eble, John N.; Cheng, Liang.

In: Cancer, Vol. 98, No. 9, 01.11.2003, p. 1830-1836.

Research output: Contribution to journalArticle

Paterson, RF, Ulbright, TM, MacLennan, GT, Zhang, S, Pan, C-X, Sweeney, CJ, Moore, CR, Foster, RS, Koch, MO, Eble, JN & Cheng, L 2003, 'Molecular Genetic Alterations in the Laser-Capture-Microdissected Stroma Adjacent to Bladder Carcinoma', Cancer, vol. 98, no. 9, pp. 1830-1836. https://doi.org/10.1002/cncr.11747
Paterson, Ryan F. ; Ulbright, Thomas M. ; MacLennan, Gregory T. ; Zhang, Shaobo ; Pan, Chong-Xian ; Sweeney, Christopher J. ; Moore, Curtiss R. ; Foster, Richard S. ; Koch, Michael O. ; Eble, John N. ; Cheng, Liang. / Molecular Genetic Alterations in the Laser-Capture-Microdissected Stroma Adjacent to Bladder Carcinoma. In: Cancer. 2003 ; Vol. 98, No. 9. pp. 1830-1836.
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abstract = "BACKGROUND. Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X-chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene. METHODS. The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin-fixed, paraffin-processed tissues using laser-assisted microdissection and LOH was determined. RESULTS. The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29{\%}), 3p25-26 (61{\%}), and 9q32-33 (47{\%}) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78{\%}) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome inactivation was frequent in the stromal cells (50{\%} of informative specimens). CONCLUSIONS. The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis.",
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AU - Paterson, Ryan F.

AU - Ulbright, Thomas M.

AU - MacLennan, Gregory T.

AU - Zhang, Shaobo

AU - Pan, Chong-Xian

AU - Sweeney, Christopher J.

AU - Moore, Curtiss R.

AU - Foster, Richard S.

AU - Koch, Michael O.

AU - Eble, John N.

AU - Cheng, Liang

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N2 - BACKGROUND. Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X-chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene. METHODS. The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin-fixed, paraffin-processed tissues using laser-assisted microdissection and LOH was determined. RESULTS. The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25-26 (61%), and 9q32-33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome inactivation was frequent in the stromal cells (50% of informative specimens). CONCLUSIONS. The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis.

AB - BACKGROUND. Urothelial carcinoma commonly manifested loss of heterozygosity (LOH) at different regions of chromosomes 17p, 3p, and 9q. Recent studies suggested that bladder stromal cells may be implicated in the growth and progression of urothelial carcinoma. To better understand the genetic alterations in the stromal cells in patients with bladder carcinoma, the authors evaluated the prevalence of allelic loss at three microsatellite polymorphic markers on chromosomes 17p13 (TP53), 3p25-26 (D3S3050), and 9q32-33 (D9S177). In addition, the pattern of X-chromosome inactivation of the stromal cells was evaluated by analyzing the DNA methylation pattern at a polymorphic site on the androgen receptor gene. METHODS. The authors studied 18 female patients who underwent either transurethral resection (n = 2) or radical cystectomy (n = 16) for high-grade muscle-invasive urothelial carcinoma of the urinary bladder. Genomic DNA samples from the stromal cells immediately adjacent to the tumor and the tumor itself were prepared from formalin-fixed, paraffin-processed tissues using laser-assisted microdissection and LOH was determined. RESULTS. The stromal cells showed a high frequency of LOH on chromosomes 17p13 (29%), 3p25-26 (61%), and 9q32-33 (47%) with no clear concordance with the adjacent tumor cells. Fourteen specimens (78%) showed LOH in the stroma in at least 1 of 3 markers examined. Nonrandom X-chromosome inactivation was frequent in the stromal cells (50% of informative specimens). CONCLUSIONS. The current study revealed that some of the genetic changes that commonly occur with invasive urothelial carcinoma were frequently found in the adjacent stroma and suggested that the stroma of urothelial carcinoma may play an important role in bladder carcinogenesis.

KW - Carcinogenesis

KW - Laser-capture microdissection

KW - Neoplasms

KW - Urinary bladder

KW - Urothelial carcinoma

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