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Identification of cytogenetic subgroups and karyotypic pathways in transitional cell carcinoma

Höglund, Mattias LU ; Säll, Torbjörn LU ; Heim, Sverre; Mitelman, Felix LU ; Mandahl, Nils LU and Fadl-Elmula, Imad (2001) In Cancer Research 61(22). p.8241-8246
Abstract
The clinical course in urinary bladder cancer is difficult or impossible to predict based on conventional disease parameters. It is a reasonable hypothesis that the genetic aberrations acquired by the tumor cells, being instrumental in bringing about the disease in the first place, may also hold the key to more reliable prognostication. However, though 200 transitional cell carcinomas (TCC), the most common bladder cancer in the Western world, with clonal chromosomal abnormalities have been reported, our knowledge about the karyotypic characteristics of these tumors remains insufficient. The aberration pattern is clearly nonrandom, but no completely specific primary or secondary karyotypic abnormality has been identified, and the... (More)
The clinical course in urinary bladder cancer is difficult or impossible to predict based on conventional disease parameters. It is a reasonable hypothesis that the genetic aberrations acquired by the tumor cells, being instrumental in bringing about the disease in the first place, may also hold the key to more reliable prognostication. However, though 200 transitional cell carcinomas (TCC), the most common bladder cancer in the Western world, with clonal chromosomal abnormalities have been reported, our knowledge about the karyotypic characteristics of these tumors remains insufficient. The aberration pattern is clearly nonrandom, but no completely specific primary or secondary karyotypic abnormality has been identified, and the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors like TCC is one reason why our picture of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties we have used several statistical methods that allow analysis and interpretation of the relationship between cytogenetic aberrations in TCC. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances and that this order is highly correlated with tumor stage and grade. Analyzing changes in the distribution of imbalances per tumor in G1, G2, and G3 tumors, we suggest that progression involves the acquisition of cytogenetically detectable and submicroscopic genetic changes at comparable frequencies. By means of computer simulations, we show that the imbalances -9, +7, and 1q+ appear earlier than expected from random events and that -6q, -5q, -18, +5p, -22p, and -15 appear later than expected. Using principal component analysis, we identify two cytogenetic pathways in TCC, one initiated by -9 and followed by -11p and 1q+, the other initiated by +7 and followed by 8p- and +8q. The -9 pathway was correlated with stage Ta-T2 tumors, whereas the +7 pathway was correlated with stage T1-T3 tumors, i.e., +7 tumors appeared to be more aggressive. Although these pathways are well separated at earlier stages, they later converge to contain a common set of imbalances. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Cancer Research
volume
61
issue
22
pages
8241 - 8246
publisher
American Association for Cancer Research Inc.
external identifiers
  • pmid:11719456
  • scopus:0035890358
ISSN
1538-7445
language
English
LU publication?
yes
id
b27d5cd5-bf37-458e-bf73-50ed61d5943b (old id 1120416)
alternative location
http://cancerres.aacrjournals.org/content/61/22/8241.abstract
date added to LUP
2008-06-30 14:31:05
date last changed
2018-06-24 04:40:22
@article{b27d5cd5-bf37-458e-bf73-50ed61d5943b,
  abstract     = {The clinical course in urinary bladder cancer is difficult or impossible to predict based on conventional disease parameters. It is a reasonable hypothesis that the genetic aberrations acquired by the tumor cells, being instrumental in bringing about the disease in the first place, may also hold the key to more reliable prognostication. However, though 200 transitional cell carcinomas (TCC), the most common bladder cancer in the Western world, with clonal chromosomal abnormalities have been reported, our knowledge about the karyotypic characteristics of these tumors remains insufficient. The aberration pattern is clearly nonrandom, but no completely specific primary or secondary karyotypic abnormality has been identified, and the chronological order in which the aberrations appear during disease progression is not well known. The high degree of karyotypic complexity in epithelial tumors like TCC is one reason why our picture of the sequential order of cytogenetic evolution is unclear. To overcome some of these difficulties we have used several statistical methods that allow analysis and interpretation of the relationship between cytogenetic aberrations in TCC. We show that there exists a temporal order with respect to the appearance of chromosomal imbalances and that this order is highly correlated with tumor stage and grade. Analyzing changes in the distribution of imbalances per tumor in G1, G2, and G3 tumors, we suggest that progression involves the acquisition of cytogenetically detectable and submicroscopic genetic changes at comparable frequencies. By means of computer simulations, we show that the imbalances -9, +7, and 1q+ appear earlier than expected from random events and that -6q, -5q, -18, +5p, -22p, and -15 appear later than expected. Using principal component analysis, we identify two cytogenetic pathways in TCC, one initiated by -9 and followed by -11p and 1q+, the other initiated by +7 and followed by 8p- and +8q. The -9 pathway was correlated with stage Ta-T2 tumors, whereas the +7 pathway was correlated with stage T1-T3 tumors, i.e., +7 tumors appeared to be more aggressive. Although these pathways are well separated at earlier stages, they later converge to contain a common set of imbalances.},
  author       = {Höglund, Mattias and Säll, Torbjörn and Heim, Sverre and Mitelman, Felix and Mandahl, Nils and Fadl-Elmula, Imad},
  issn         = {1538-7445},
  language     = {eng},
  number       = {22},
  pages        = {8241--8246},
  publisher    = {American Association for Cancer Research Inc.},
  series       = {Cancer Research},
  title        = {Identification of cytogenetic subgroups and karyotypic pathways in transitional cell carcinoma},
  volume       = {61},
  year         = {2001},
}