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Characterization and drug sensitivity of a novel human overian clear cell carcinoma cell line genomically and phenotypically similar to the original tumor

Lookup NU author(s): Lucy Gentles, Liz Matheson, Dr Nicholas Bown, Alice Bradbury, Maryam Zanjirband Zanjirband, Professor John LunecORCiD, Dr Yvette DrewORCiD, Dr Rachel O'DonnellORCiD, Professor Nicola CurtinORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).


Abstract

AbstractNUCOLL43 is a novel ovarian clear cell carcinoma (O‐CCC) cell line that arose from a primary culture of a patient's malignant ascites. The cells grow reliably in cell culture with a doubling time of approx. 45 hours and form colonies at high efficiency. They have a very high degree of loss of heterozygosity (LOH) affecting approximately 85% of the genome, mostly copy neutral and almost identical to the original tumor. The cells express epithelial (pan‐cytokeratin) and mesenchymal (vimentin) characteristics, CA125 and p16, like the original tumor. They also express ARID1A but not HNF‐1β and, like the original tumor, and are negative for p53 expression, with no evidence of p53 function. NUCOLL43 cells express all other DNA damage response proteins investigated and have functional homologous recombination DNA repair. They are insensitive to cisplatin, the PARP inhibitor rucaparib, and MDM2 inhibitors but are sensitive to camptothecin, paclitaxel, and NVP‐BEZ235. The NUCOLL43 cell line represents a distinct subtype of O‐CCC that is p53 and HNF‐1β null but expresses ARID1A. Its high degree of similarity with the original tumor genomically and proteomically, as well as the high level of LOH, make this an interesting cell line for O‐CCC research. It has been deposited with Ximbio.


Publication metadata

Author(s): Franklin M, Gentles L, Matheson E, Bown N, Cross P, Ralte A, Gilkes-Immeson C, Bradbury A, Zanjirband M, Lunec J, Drew Y, O'Donnell R, Curtin NJ

Publication type: Article

Publication status: Published

Journal: Cancer Medicine

Year: 2018

Volume: 7

Issue: 9

Pages: 4744-4754

Print publication date: 01/09/2018

Online publication date: 14/08/2018

Acceptance date: 16/07/2018

Date deposited: 22/08/2018

ISSN (electronic): 2045-7634

Publisher: John Wiley & Sons Ltd.

URL: https://doi.org/10.1002/cam4.1724

DOI: 10.1002/cam4.1724


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Funding

Funder referenceFunder name
Northern Cancer Care and Research Society
Wellcome vacation scholarship Scheme

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