Two molecular pathways to transitional cell carcinoma of the bladder

Charles H. Spruck, Petra F. Ohneseit, Mirella Gonzalez-Zulueta, David Esrig, Noriomi Miyao, Yvonne C. Tsai, Seth P. Lerner, Christoph Schmütte, Allen S. Yang, Richard J Cote, Louis Dubeau, Peter W. Nichols, Gregers G. Hermann, Kenneth Steven, Thomas Horn, Donald G. Skinner, Peter A. Jones

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Abstract

Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34%) T(a) tumors but was present in only 3 of 24 (12%) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3%) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65%) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51%). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.

Original languageEnglish
Pages (from-to)784-788
Number of pages5
JournalCancer Research
Volume54
Issue number3
StatePublished - Feb 1 1994
Externally publishedYes

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Transitional Cell Carcinoma
Urinary Bladder
Carcinoma in Situ
Neoplasms
Chromosomes, Human, Pair 9
Mutation
Carcinogenesis
Loss of Heterozygosity
Papillary Carcinoma
p53 Genes
Urinary Bladder Neoplasms
Genome
Pathology

ASJC Scopus subject areas

  • Cancer Research
  • Oncology

Cite this

Spruck, C. H., Ohneseit, P. F., Gonzalez-Zulueta, M., Esrig, D., Miyao, N., Tsai, Y. C., ... Jones, P. A. (1994). Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Research, 54(3), 784-788.

Two molecular pathways to transitional cell carcinoma of the bladder. / Spruck, Charles H.; Ohneseit, Petra F.; Gonzalez-Zulueta, Mirella; Esrig, David; Miyao, Noriomi; Tsai, Yvonne C.; Lerner, Seth P.; Schmütte, Christoph; Yang, Allen S.; Cote, Richard J; Dubeau, Louis; Nichols, Peter W.; Hermann, Gregers G.; Steven, Kenneth; Horn, Thomas; Skinner, Donald G.; Jones, Peter A.

In: Cancer Research, Vol. 54, No. 3, 01.02.1994, p. 784-788.

Research output: Contribution to journalArticle

Spruck, CH, Ohneseit, PF, Gonzalez-Zulueta, M, Esrig, D, Miyao, N, Tsai, YC, Lerner, SP, Schmütte, C, Yang, AS, Cote, RJ, Dubeau, L, Nichols, PW, Hermann, GG, Steven, K, Horn, T, Skinner, DG & Jones, PA 1994, 'Two molecular pathways to transitional cell carcinoma of the bladder', Cancer Research, vol. 54, no. 3, pp. 784-788.
Spruck CH, Ohneseit PF, Gonzalez-Zulueta M, Esrig D, Miyao N, Tsai YC et al. Two molecular pathways to transitional cell carcinoma of the bladder. Cancer Research. 1994 Feb 1;54(3):784-788.
Spruck, Charles H. ; Ohneseit, Petra F. ; Gonzalez-Zulueta, Mirella ; Esrig, David ; Miyao, Noriomi ; Tsai, Yvonne C. ; Lerner, Seth P. ; Schmütte, Christoph ; Yang, Allen S. ; Cote, Richard J ; Dubeau, Louis ; Nichols, Peter W. ; Hermann, Gregers G. ; Steven, Kenneth ; Horn, Thomas ; Skinner, Donald G. ; Jones, Peter A. / Two molecular pathways to transitional cell carcinoma of the bladder. In: Cancer Research. 1994 ; Vol. 54, No. 3. pp. 784-788.
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abstract = "Noninvasive transitional cell carcinomas of the bladder can have two distinct morphologies suggesting they contain different genetic alterations. Papillary transitional cell carcinomas (T(a) tumors) are often multifocal and only occasionally progress, whereas flat tumors (carcinomas in situ, CIS), frequently progress to invasive disease. We examined 216 bladder tumors of various stages and histopathologies for two genetic alterations previously described to be of importance in bladder tumorigenesis. Loss of heterozygosity of chromosome 9 was observed in 24 of 70 (34{\%}) T(a) tumors but was present in only 3 of 24 (12{\%}) CIS and dysplasia lesions (P = 0.04). In contrast, only 1 of 36 (3{\%}) T(a) tumors contained a p53 gene mutation compared to 15 of 23 (65{\%}) CIS and dysplasias (P < 0.001), a frequency comparable to that observed in muscle invasive tumors (25 of 49; 51{\%}). The presence of p53 mutations in CIS and dysplasia could explain their propensities to progress since these mutations are known to destabilize the genome. Analysis of several tumor pairs involving a CIS and an invasive cancer provided evidence that the chromosome 9 alteration may in some cases be involved in the progression of CIS to more invasive tumors, in addition to its role in the initiation of T(a) tumors. However, the CIS and secondary tumor were found to contain different genetic alterations in some patients suggesting divergent progression pathways. Bladder carcinogenesis may therefore proceed through two distinct genetic alteration pathways responsible for generating superficial tumors with differing morphologies and pathologies.",
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AU - Cote, Richard J

AU - Dubeau, Louis

AU - Nichols, Peter W.

AU - Hermann, Gregers G.

AU - Steven, Kenneth

AU - Horn, Thomas

AU - Skinner, Donald G.

AU - Jones, Peter A.

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