The UBC-40 Urothelial Bladder Cancer cell line index: A genomic resource for functional studies

Julie Earl, Daniel Rico, Enrique Carrillo-de-Santa-Pau, Benjamín Rodríguez-Santiago, Marinela Méndez-Pertuz, Herbert Auer, Gonzalo Gómez, Herbert Barton Grossman, David G. Pisano, Wolfgang A. Schulz, Luis Perez-Jurado, Alfredo Carrato, Dan Theodorescu, Stephen Chanock, Alfonso Valencia, Francisco X. Real

Research output: Contribution to journalArticle

38 Citations (Scopus)

Abstract

Background: Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Results: Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Conclusions: Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.

LanguageEnglish
Article number403
JournalBMC Genomics
Volume16
Issue number1
DOIs
Publication statusPublished - 22 May 2015
Externally publishedYes

Keywords

  • Cell line
  • Genomics
  • Mutation
  • Oncogene
  • Tumor suppressor
  • Urothelial bladder cancer

ASJC Scopus subject areas

  • Biotechnology
  • Genetics

Cite this

Earl, J., Rico, D., Carrillo-de-Santa-Pau, E., Rodríguez-Santiago, B., Méndez-Pertuz, M., Auer, H., ... Real, F. X. (2015). The UBC-40 Urothelial Bladder Cancer cell line index: A genomic resource for functional studies. BMC Genomics, 16(1), [403]. https://doi.org/10.1186/s12864-015-1450-3
Earl, Julie ; Rico, Daniel ; Carrillo-de-Santa-Pau, Enrique ; Rodríguez-Santiago, Benjamín ; Méndez-Pertuz, Marinela ; Auer, Herbert ; Gómez, Gonzalo ; Grossman, Herbert Barton ; Pisano, David G. ; Schulz, Wolfgang A. ; Perez-Jurado, Luis ; Carrato, Alfredo ; Theodorescu, Dan ; Chanock, Stephen ; Valencia, Alfonso ; Real, Francisco X. / The UBC-40 Urothelial Bladder Cancer cell line index : A genomic resource for functional studies. In: BMC Genomics. 2015 ; Vol. 16, No. 1.
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Earl, J, Rico, D, Carrillo-de-Santa-Pau, E, Rodríguez-Santiago, B, Méndez-Pertuz, M, Auer, H, Gómez, G, Grossman, HB, Pisano, DG, Schulz, WA, Perez-Jurado, L, Carrato, A, Theodorescu, D, Chanock, S, Valencia, A & Real, FX 2015, 'The UBC-40 Urothelial Bladder Cancer cell line index: A genomic resource for functional studies', BMC Genomics, vol. 16, no. 1, 403. https://doi.org/10.1186/s12864-015-1450-3

The UBC-40 Urothelial Bladder Cancer cell line index : A genomic resource for functional studies. / Earl, Julie; Rico, Daniel; Carrillo-de-Santa-Pau, Enrique; Rodríguez-Santiago, Benjamín; Méndez-Pertuz, Marinela; Auer, Herbert; Gómez, Gonzalo; Grossman, Herbert Barton; Pisano, David G.; Schulz, Wolfgang A.; Perez-Jurado, Luis; Carrato, Alfredo; Theodorescu, Dan; Chanock, Stephen; Valencia, Alfonso; Real, Francisco X.

In: BMC Genomics, Vol. 16, No. 1, 403, 22.05.2015.

Research output: Contribution to journalArticle

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T1 - The UBC-40 Urothelial Bladder Cancer cell line index

T2 - BMC Genomics

AU - Earl, Julie

AU - Rico, Daniel

AU - Carrillo-de-Santa-Pau, Enrique

AU - Rodríguez-Santiago, Benjamín

AU - Méndez-Pertuz, Marinela

AU - Auer, Herbert

AU - Gómez, Gonzalo

AU - Grossman, Herbert Barton

AU - Pisano, David G.

AU - Schulz, Wolfgang A.

AU - Perez-Jurado, Luis

AU - Carrato, Alfredo

AU - Theodorescu, Dan

AU - Chanock, Stephen

AU - Valencia, Alfonso

AU - Real, Francisco X.

PY - 2015/5/22

Y1 - 2015/5/22

N2 - Background: Urothelial bladder cancer is a highly heterogeneous disease. Cancer cell lines are useful tools for its study. This is a comprehensive genomic characterization of 40 urothelial bladder carcinoma (UBC) cell lines including information on origin, mutation status of genes implicated in bladder cancer (FGFR3, PIK3CA, TP53, and RAS), copy number alterations assessed using high density SNP arrays, uniparental disomy (UPD) events, and gene expression. Results: Based on gene mutation patterns and genomic changes we identify lines representative of the FGFR3-driven tumor pathway and of the TP53/RB tumor suppressor-driven pathway. High-density array copy number analysis identified significant focal gains (1q32, 5p13.1-12, 7q11, and 7q33) and losses (i.e. 6p22.1) in regions altered in tumors but not previously described as affected in bladder cell lines. We also identify new evidence for frequent regions of UPD, often coinciding with regions reported to be lost in tumors. Previously undescribed chromosome X losses found in UBC lines also point to potential tumor suppressor genes. Cell lines representative of the FGFR3-driven pathway showed a lower number of UPD events. Conclusions: Overall, there is a predominance of more aggressive tumor subtypes among the cell lines. We provide a cell line classification that establishes their relatedness to the major molecularly-defined bladder tumor subtypes. The compiled information should serve as a useful reference to the bladder cancer research community and should help to select cell lines appropriate for the functional analysis of bladder cancer genes, for example those being identified through massive parallel sequencing.

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KW - Cell line

KW - Genomics

KW - Mutation

KW - Oncogene

KW - Tumor suppressor

KW - Urothelial bladder cancer

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Earl J, Rico D, Carrillo-de-Santa-Pau E, Rodríguez-Santiago B, Méndez-Pertuz M, Auer H et al. The UBC-40 Urothelial Bladder Cancer cell line index: A genomic resource for functional studies. BMC Genomics. 2015 May 22;16(1). 403. https://doi.org/10.1186/s12864-015-1450-3