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UOK171, A Spontaneous Clear Cell Type Renal Cell Carcinoma (ccRCC) Human Cell Line Derived from a Surgically Removed Tumor

Posted Jun 06 2010 5:00pm

Description of Invention:
Scientists at the National Institutes of Health (NIH) have developed a renal cell carcinoma (RCC) cell line designated UOK171 from the resected tumor of a patient diagnosed with stage IV high nuclear grade clear cell type renal cell carcinoma (ccRCC). The UOK171 cell line was immortalized spontaneously by mincing the resected tumor into pieces followed by propagation of the cells over more than twenty generations. One of the most prominent characteristics of this cell line is its intact, nonmutated von Hippel-Lindau (VHL) tumor suppressor gene. In the majority of sporadic and hereditary ccRCC cases, the VHL gene is functionally disrupted due to hypermethylation or the gene is completely lost. Thus, the UOK171 cell line is very useful as a positive control for VHL gene expression in studies of the genetic and molecular mechanisms underlying advanced ccRCC, a disease for which there is no effective treatment. Specifically, this cell line has been used as a non-methylated control cell line in studying the effects of 5-Aza-dCyd and Zebularine on VHL re-expression from methylated-VHL cell line models. These agents do not affect the methylation status of the VHL gene in UOK171. This cell line also exhibits decreased fibroblast growth factor 5 (FGF5) expression, unbalanced chromosome 3 translocations, translocations involving chromosome 14, the losses of chromosome 14 and 22, and chromosome structural aberration 1(8) (q10). UOK171 is also one of the 40-member cell lines in the National Cancer Institute (NCI) Urologic Oncology Branch (UOB) Tumor Cell Line Repository.

Applications:
  • Research tool for investigating the underlying molecular mechanisms contributing to advanced ccRCC, including the identification of new RCC tumor antigens for immunotherapy
  • Research tool for studying the methylation status of genes involved in ccRCC to reveal the genetic processes occurring in ccRCC tissues that may contribute to advanced disease
  • Positive control cell line for VHL gene expression and function studies, including cytogenetics, gene mutation research, and examination of chromosomal structural abnormalities that may contribute to ccRCC
  • Research tools for testing the activity of potential anti-cancer drugs against ccRCC, a disease which has no effective treatment options
  • Possible starting material for developing a cancer vaccine against RCC


Advantages:
  • Cell line is derived from a ccRCC patient: These cell lines are anticipated to retain many features of primary ccRCC samples and novel ccRCC antigens identified from this cell line are likely to correlate with antigens expressed on human ccRCC tumors. Studies performed using these cell lines may have a direct correlation to the initiation, progression, treatment, and prevention of ccRCC in humans.
  • Expresses a non-mutated VHL gene: In the majority of advanced ccRCC patients the VHL gene has been mutated or deleted. The UOK171 cell line represents a tool that can be utilized to study the impact of this VHL gene and various mutations on advanced ccRCC.
  • Molecular and genetic features are well characterized: This cell line is part of NCI Urologic Oncology Branch's Tumor Cell Line Repository. The inventor has elucidated many physical characteristics of the cell line, including chromosomal attributes and important ccRCC genes, under various conditions.


Inventors:
W Marston Linehan (NCI)


Patent Status:
HHS, Reference No. E-033-2010/0

Research Tool -- patent protection is not being pursued for this technology

Relevant Publication:
  1. WG Alleman et al. The in vitro and in vivo effects of re-expressing methylated von Hippel-Lindau tumor suppressor gene in clear cell renal carcinoma with 5-Aza-2'-deoxycytidine. Clin Cancer Res. 2004 Oct 15;10(20):7011-7021. [ PubMed: 15501981 ]
  2. CP Pavlovich et al. Patterns of aneuploidy in stage IV clear cell renal carcinoma revealed comparative genomic hybridization and spectral karyotyping. Genes Chromosomes Cancer. 2003 Jul;37(3):252-260. [ PubMed: 12759923 ]
  3. K Hanada et al. Identification of fibroblast growth factor-5 as an overexpressed antigen in multiple human adenocarcinomas. Cancer Res. 2001 Jul 15;61(14):5511-5516. [ PubMed: 11454700 ]
  4. C Stolle et al. Improved detection of germline mutations in the von Hippel-Lindau disease tumor suppressor gene. Hum Mutat. 1998;12(6):417-423. [ PubMed: 9829911 ]
  5. P Anglard et al. Molecular and cellular characterization of human renal cell carcinoma cell lines. Cancer Res. 1992 Jan 15;52(2):348-356. [ PubMed: 1345811 ]


Licensing Status:
Available for licensing under a Biological Materials License Agreement.

Collaborative Research Opportunity:
The Urologic Oncology Branch, Center for Cancer Research, is seeking statements of capability or interest from parties interested in collaborative research to further develop, evaluate, or commercialize UOK171. Please contact John Hewes, Ph.D. at 301-435-3121 or hewesj@mail.nih.gov for more information.


Portfolios:
Devices/Instrumentation
Devices/Instrumentation - Research Tools and Materials
Cancer
Cancer - Research Materials



For Additional Information Please Contact:
Samuel Bish Ph.D.
NIH Office of Technology Transfer
6011 Executive Blvd. Suite 325,
Rockville, MD 20852
United States
Email: bishse@mail.nih.gov
Phone: 301-435-5282
Fax: 301-402-0220


Ref No: 2116

Updated: 06/2010

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