Small-cell Carcinomas of the Urinary Bladder and Prostate

TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma

David Priemer, Mingsheng Wang, Shaobo Zhang, Antonio Lopez-Beltran, Erik Kouba, Rodolfo Montironi, Darrell D. Davidson, Gregory T. MacLennan, Lisha Wang, Adeboye O. Osunkoya, Youping Deng, Robert E. Emerson, Liang Cheng

Research output: Contribution to journalArticle

Abstract

Background: Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. Objective: To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. Design, setting, and participants: We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. Outcome measurements and statistical analysis: We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. Results and limitations: TERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non–small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. Conclusions: TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Patient summary: Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma.

Original languageEnglish (US)
Pages (from-to)880-888
Number of pages9
JournalEuropean Urology Focus
Volume4
Issue number6
DOIs
StatePublished - Dec 1 2018
Externally publishedYes

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Small Cell Carcinoma
Prostate
Urinary Bladder
Carcinoma
Mutation
Neoplasms
Cellular Structures
Carcinogenesis

Keywords

  • Bladder
  • Histogenesis
  • Small-cell carcinoma
  • Telomerase reverse transcriptase (TERT)
  • Tumor heterogeneity

ASJC Scopus subject areas

  • Urology

Cite this

Small-cell Carcinomas of the Urinary Bladder and Prostate : TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma. / Priemer, David; Wang, Mingsheng; Zhang, Shaobo; Lopez-Beltran, Antonio; Kouba, Erik; Montironi, Rodolfo; Davidson, Darrell D.; MacLennan, Gregory T.; Wang, Lisha; Osunkoya, Adeboye O.; Deng, Youping; Emerson, Robert E.; Cheng, Liang.

In: European Urology Focus, Vol. 4, No. 6, 01.12.2018, p. 880-888.

Research output: Contribution to journalArticle

Priemer, David ; Wang, Mingsheng ; Zhang, Shaobo ; Lopez-Beltran, Antonio ; Kouba, Erik ; Montironi, Rodolfo ; Davidson, Darrell D. ; MacLennan, Gregory T. ; Wang, Lisha ; Osunkoya, Adeboye O. ; Deng, Youping ; Emerson, Robert E. ; Cheng, Liang. / Small-cell Carcinomas of the Urinary Bladder and Prostate : TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma. In: European Urology Focus. 2018 ; Vol. 4, No. 6. pp. 880-888.
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abstract = "Background: Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. Objective: To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. Design, setting, and participants: We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. Outcome measurements and statistical analysis: We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. Results and limitations: TERT promoter mutations were detected in 29/53 (55{\%}) cases of urinary bladder and 0/26 (0{\%}) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non–small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. Conclusions: TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Patient summary: Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma.",
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T2 - TERT Promoter Mutation Status Differentiates Sites of Malignancy and Provides Evidence of Common Clonality Between Small-cell Carcinoma of the Urinary Bladder and Urothelial Carcinoma

AU - Priemer, David

AU - Wang, Mingsheng

AU - Zhang, Shaobo

AU - Lopez-Beltran, Antonio

AU - Kouba, Erik

AU - Montironi, Rodolfo

AU - Davidson, Darrell D.

AU - MacLennan, Gregory T.

AU - Wang, Lisha

AU - Osunkoya, Adeboye O.

AU - Deng, Youping

AU - Emerson, Robert E.

AU - Cheng, Liang

PY - 2018/12/1

Y1 - 2018/12/1

N2 - Background: Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. Objective: To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. Design, setting, and participants: We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. Outcome measurements and statistical analysis: We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. Results and limitations: TERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non–small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. Conclusions: TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Patient summary: Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma.

AB - Background: Small-cell carcinoma (SCC) of the urinary bladder frequently appears alongside urothelial carcinoma, suggesting common clonality. TERT promoter mutations have been recently implicated in urothelial carcinogenesis. Objective: To investigate the degree to which TERT promoter mutations are involved in SCC of the urinary bladder, the linked tumorigenesis between urothelial carcinoma and SCC of the urinary bladder, and the molecular distinctions between SCC of the urinary bladder and of the prostate. Design, setting, and participants: We investigated TERT promoter mutations in 53 cases of SCC of the urinary bladder and in 26 cases of SCC of the prostate using laboratory-based studies of tissue samples and clinical data. Outcome measurements and statistical analysis: We measured the frequency of TERT promoter mutations in SCCs of the urinary bladder and prostate, and concordance of the mutation status between concurrent urinary bladder SCC and urothelial carcinoma. Results and limitations: TERT promoter mutations were detected in 29/53 (55%) cases of urinary bladder and 0/26 (0%) cases of prostate SCC. Of 25 cases with concurrent urinary bladder SCC and non–small-cell components, all cases harbored identical TERT promoter mutation status in both phenotypes. Conclusions: TERT promoter mutations are found in more than half of urinary bladder SCCs. Mutation status is also identical in urothelial carcinoma and SCC components of concomitant malignancies, providing evidence of a common clonality. TERT promoter mutation status can differentiate SCC of the urinary bladder from prostate SCC, suggesting potential diagnostic use. Patient summary: Small-cell carcinoma of the urinary bladder shares a common clonal origin with conventional urothelial carcinoma and may arise from a heterogeneous subclone. TERT promoter mutations may have utility as a differential biomarker for determining the primary site of a genitourinary small-cell carcinoma.

KW - Bladder

KW - Histogenesis

KW - Small-cell carcinoma

KW - Telomerase reverse transcriptase (TERT)

KW - Tumor heterogeneity

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