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A Molecular Taxonomy for Urothelial Carcinoma.

Sjödahl, Gottfrid LU ; Lauss, Martin LU ; Lövgren, Kristina LU ; Chebil, Gunilla; Gudjonsson, Sigurdur LU ; Veerla, Srinivas; Hultman Patschan, Oliver LU ; Aine, Mattias LU ; Fernö, Mårten LU and Ringnér, Markus LU , et al. (2012) In Clinical Cancer Research 18(12). p.3377-3386
Abstract
PURPOSE:

Even though urothelial cancer is the fourth most common tumor type among males, progress in treatment has been scarce. A problem in day-to-day clinical practice is that precise assessment of individual tumors is still fairly uncertain; consequently efforts have been undertaken to complement tumor evaluation with molecular biomarkers. An extension of this approach would be to base tumor classification primarily on molecular features. Here, we present a molecular taxonomy for urothelial carcinoma based on integrated genomics.



EXPERIMENTAL DESIGN:

We use gene expression profiles from 308 tumor cases to define five major urothelial carcinoma subtypes: urobasal A, genomically unstable, urobasal B,... (More)
PURPOSE:

Even though urothelial cancer is the fourth most common tumor type among males, progress in treatment has been scarce. A problem in day-to-day clinical practice is that precise assessment of individual tumors is still fairly uncertain; consequently efforts have been undertaken to complement tumor evaluation with molecular biomarkers. An extension of this approach would be to base tumor classification primarily on molecular features. Here, we present a molecular taxonomy for urothelial carcinoma based on integrated genomics.



EXPERIMENTAL DESIGN:

We use gene expression profiles from 308 tumor cases to define five major urothelial carcinoma subtypes: urobasal A, genomically unstable, urobasal B, squamous cell carcinoma like, and an infiltrated class of tumors. Tumor subtypes were validated in three independent publically available data sets. The expression of 11 key genes was validated at the protein level by immunohistochemistry.



RESULTS:

The subtypes show distinct clinical outcomes and differ with respect to expression of cell-cycle genes, receptor tyrosine kinases particularly FGFR3, ERBB2, and EGFR, cytokeratins, and cell adhesion genes, as well as with respect to FGFR3, PIK3CA, and TP53 mutation frequency. The molecular subtypes cut across pathologic classification, and class-defining gene signatures show coordinated expression irrespective of pathologic stage and grade, suggesting the molecular phenotypes as intrinsic properties of the tumors. Available data indicate that susceptibility to specific drugs is more likely to be associated with the molecular stratification than with pathologic classification.



CONCLUSIONS:

We anticipate that the molecular taxonomy will be useful in future clinical investigations. Clin Cancer Res; 1-10. ©2012 AACR. (Less)
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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Clinical Cancer Research
volume
18
issue
12
pages
3377 - 3386
publisher
American Association for Cancer Research
external identifiers
  • wos:000307502100018
  • pmid:22553347
  • scopus:84862576866
ISSN
1078-0432
DOI
10.1158/1078-0432.CCR-12-0077-T
language
English
LU publication?
yes
id
2dad18db-5e2e-49a8-8da7-dacc49a8cd0a (old id 2609207)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/22553347?dopt=Abstract
date added to LUP
2012-06-02 16:24:46
date last changed
2017-11-19 03:10:21
@article{2dad18db-5e2e-49a8-8da7-dacc49a8cd0a,
  abstract     = {PURPOSE: <br/><br>
Even though urothelial cancer is the fourth most common tumor type among males, progress in treatment has been scarce. A problem in day-to-day clinical practice is that precise assessment of individual tumors is still fairly uncertain; consequently efforts have been undertaken to complement tumor evaluation with molecular biomarkers. An extension of this approach would be to base tumor classification primarily on molecular features. Here, we present a molecular taxonomy for urothelial carcinoma based on integrated genomics.<br/><br>
<br/><br>
EXPERIMENTAL DESIGN: <br/><br>
We use gene expression profiles from 308 tumor cases to define five major urothelial carcinoma subtypes: urobasal A, genomically unstable, urobasal B, squamous cell carcinoma like, and an infiltrated class of tumors. Tumor subtypes were validated in three independent publically available data sets. The expression of 11 key genes was validated at the protein level by immunohistochemistry.<br/><br>
<br/><br>
RESULTS: <br/><br>
The subtypes show distinct clinical outcomes and differ with respect to expression of cell-cycle genes, receptor tyrosine kinases particularly FGFR3, ERBB2, and EGFR, cytokeratins, and cell adhesion genes, as well as with respect to FGFR3, PIK3CA, and TP53 mutation frequency. The molecular subtypes cut across pathologic classification, and class-defining gene signatures show coordinated expression irrespective of pathologic stage and grade, suggesting the molecular phenotypes as intrinsic properties of the tumors. Available data indicate that susceptibility to specific drugs is more likely to be associated with the molecular stratification than with pathologic classification.<br/><br>
<br/><br>
CONCLUSIONS: <br/><br>
We anticipate that the molecular taxonomy will be useful in future clinical investigations. Clin Cancer Res; 1-10. ©2012 AACR.},
  author       = {Sjödahl, Gottfrid and Lauss, Martin and Lövgren, Kristina and Chebil, Gunilla and Gudjonsson, Sigurdur and Veerla, Srinivas and Hultman Patschan, Oliver and Aine, Mattias and Fernö, Mårten and Ringnér, Markus and Månsson, Wiking and Liedberg, Fredrik and Lindgren, David and Höglund, Mattias},
  issn         = {1078-0432},
  language     = {eng},
  number       = {12},
  pages        = {3377--3386},
  publisher    = {American Association for Cancer Research},
  series       = {Clinical Cancer Research},
  title        = {A Molecular Taxonomy for Urothelial Carcinoma.},
  url          = {http://dx.doi.org/10.1158/1078-0432.CCR-12-0077-T},
  volume       = {18},
  year         = {2012},
}