Genomic and metabolic characterization of a chromophobe renal cell carcinoma cell line model (UOK276)
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Updated: Feb 26, 2026
Comparing Metastatic Clear Cell Renal Cell Carcinoma Model Established in Mouse Kidney and on Chicken Chorioallantoic Membrane
Published on: February 8, 2020
Youfeng Yang1, Cathy D Vocke1, Christopher J Ricketts1
1Urologic Oncology Branch, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, Maryland.
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.
Insights
A new cell line model, UOK276, derived from chromophobe renal cell carcinoma (ChRCC) with sarcomatoid features, has been characterized. This model exhibits TP53 mutations and responds to targeted therapy, offering a valuable tool for studying aggressive ChRCC.
Area of Science:
- Oncology
- Cancer Biology
- Genitourinary Pathology
Background:
- Chromophobe renal cell carcinoma (ChRCC) is a rare kidney cancer subtype with variable clinical behavior.
- Existing ChRCC cell lines are limited, hindering research into its biology and treatment.
- Aggressive ChRCC subtypes, particularly those with sarcomatoid differentiation, require better preclinical models.
Purpose of the Study:
- To characterize a novel cell line, UOK276, derived from a chromophobe renal cell carcinoma with sarcomatoid features.
- To evaluate the genetic, chromosomal, and metabolic profile of the UOK276 cell line.
- To establish UOK276 as a preclinical model for investigating aggressive ChRCC.
Main Methods:
- Establishment of a spontaneously immortalized cell line (UOK276) from a ChRCC tumor with sarcomatoid differentiation.
- Comprehensive analysis of chromosomal aberrations, TP53 mutational status, and protein expression.
- In vivo validation using xenograft models in nude mice.
- Assessment of therapeutic response to a TP53-reactivating agent (NSC319726).
Main Results:
- UOK276 cells are hyperdiploid with a modal chromosome number of 49 and exhibit copy-neutral loss of heterozygosity.
- A TP53 missense mutation was identified in UOK276, with corresponding mutant TP53 protein expression.
- UOK276 cells responded to the small-molecule therapeutic agent NSC319726.
- Xenograft tumors derived from UOK276 showed pathology consistent with sarcomatoid differentiation and suggested derivation from the sarcomatoid component of the original tumor.
Conclusions:
- UOK276 represents a novel, well-characterized cell line model for aggressive, sarcomatoid-differentiated, TP53-mutant ChRCC.
- This in vitro and in vivo model provides a valuable platform for studying the unique biology of aggressive ChRCC.
- The UOK276 model can be utilized for evaluating novel therapeutic strategies against ChRCC with sarcomatoid features and TP53 mutations.
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