Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276)

Youfeng Yang, Cathy D. Vocke, Christopher J. Ricketts, Darmood Wei, Hesed M. Padilla-Nash, Martin Lang, Carole Sourbier, J. Keith Killian, Shawna L Boyle, Robert Worrell, Paul S. Meltzer, Thomas Ried, Maria J. Merino, Adam R. Metwalli, W. Marston Linehan

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.

Original languageEnglish (US)
Pages (from-to)719-729
Number of pages11
JournalGenes Chromosomes and Cancer
Volume56
Issue number10
DOIs
StatePublished - Oct 1 2017
Externally publishedYes

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Renal Cell Carcinoma
Cell Line
Heterografts
Neoplasms
Tumor Suppressor Protein p53
Polyploidy
Loss of Heterozygosity
Missense Mutation
Mutant Proteins
Therapeutics
Nude Mice
Animal Models
Chromosomes
Pathology
Growth
Pharmaceutical Preparations

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Yang, Y., Vocke, C. D., Ricketts, C. J., Wei, D., Padilla-Nash, H. M., Lang, M., ... Linehan, W. M. (2017). Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276). Genes Chromosomes and Cancer, 56(10), 719-729. https://doi.org/10.1002/gcc.22476

Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276). / Yang, Youfeng; Vocke, Cathy D.; Ricketts, Christopher J.; Wei, Darmood; Padilla-Nash, Hesed M.; Lang, Martin; Sourbier, Carole; Killian, J. Keith; Boyle, Shawna L; Worrell, Robert; Meltzer, Paul S.; Ried, Thomas; Merino, Maria J.; Metwalli, Adam R.; Linehan, W. Marston.

In: Genes Chromosomes and Cancer, Vol. 56, No. 10, 01.10.2017, p. 719-729.

Research output: Contribution to journalArticle

Yang, Y, Vocke, CD, Ricketts, CJ, Wei, D, Padilla-Nash, HM, Lang, M, Sourbier, C, Killian, JK, Boyle, SL, Worrell, R, Meltzer, PS, Ried, T, Merino, MJ, Metwalli, AR & Linehan, WM 2017, 'Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276)', Genes Chromosomes and Cancer, vol. 56, no. 10, pp. 719-729. https://doi.org/10.1002/gcc.22476
Yang, Youfeng ; Vocke, Cathy D. ; Ricketts, Christopher J. ; Wei, Darmood ; Padilla-Nash, Hesed M. ; Lang, Martin ; Sourbier, Carole ; Killian, J. Keith ; Boyle, Shawna L ; Worrell, Robert ; Meltzer, Paul S. ; Ried, Thomas ; Merino, Maria J. ; Metwalli, Adam R. ; Linehan, W. Marston. / Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276). In: Genes Chromosomes and Cancer. 2017 ; Vol. 56, No. 10. pp. 719-729.
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abstract = "Chromophobe renal cell carcinoma (ChRCC) represents 5{\%} of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.",
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AU - Vocke, Cathy D.

AU - Ricketts, Christopher J.

AU - Wei, Darmood

AU - Padilla-Nash, Hesed M.

AU - Lang, Martin

AU - Sourbier, Carole

AU - Killian, J. Keith

AU - Boyle, Shawna L

AU - Worrell, Robert

AU - Meltzer, Paul S.

AU - Ried, Thomas

AU - Merino, Maria J.

AU - Metwalli, Adam R.

AU - Linehan, W. Marston

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N2 - Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.

AB - Chromophobe renal cell carcinoma (ChRCC) represents 5% of all RCC cases and frequently demonstrates multiple chromosomal losses and an indolent pattern of local growth, but can demonstrate aggressive features and resistance to treatment in a metastatic setting. Cell line models are an important tool for the investigation of tumor biology and therapeutic drug efficacy. Currently, there are few ChRCC-derived cell lines and none is well characterized. This study characterizes a novel ChRCC-derived cell line model, UOK276. A large ChRCC tumor with regions of sarcomatoid differentiation was used to establish a spontaneously immortal cell line, UOK276. UOK276 was evaluated for chromosomal, mutational, and metabolic aberrations. The UOK276 cell line is hyperdiploid with a modal number of 49 chromosomes per cell, and evidence of copy-neutral loss of heterozygosity, as opposed to the classic pattern of ChRCC chromosomal losses. UOK276 demonstrated a TP53 missense mutation, expressed mutant TP53 protein, and responded to treatment with a small-molecule therapeutic agent, NSC319726, designed to reactivate mutated TP53. Xenograft tumors grew in nude mice and provide an in vivo animal model for the investigation of potential therapeutic regimes. The xenograft pathology and genetic analysis suggested that UOK276 was derived from the sarcomatoid region of the original tumor. In summary, UOK276 represents a novel in vitro and in vivo cell line model for aggressive, sarcomatoid-differentiated, TP53 mutant ChRCC. This preclinical model system could be used to investigate the novel biology of aggressive, sarcomatoid ChRCC and evaluate the new therapeutic regimes.

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