Article

Evaluating cell lines as tumour models by comparison of genomic profiles

1] Computational Biology Center, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, Box 460, New York, New York 10065, USA [2] Department of Chemistry, Technische Universität München, Lichtenbergstraße 4, 85747 Garching bei München, Germany [3].
Nature Communications (Impact Factor: 11.47). 07/2013; 4:2126. DOI: 10.1038/ncomms3126
Source: PubMed

ABSTRACT

Cancer cell lines are frequently used as in vitro tumour models. Recent molecular profiles of hundreds of cell lines from The Cancer Cell Line Encyclopedia and thousands of tumour samples from the Cancer Genome Atlas now allow a systematic genomic comparison of cell lines and tumours. Here we analyse a panel of 47 ovarian cancer cell lines and identify those that have the highest genetic similarity to ovarian tumours. Our comparison of copy-number changes, mutations and mRNA expression profiles reveals pronounced differences in molecular profiles between commonly used ovarian cancer cell lines and high-grade serous ovarian cancer tumour samples. We identify several rarely used cell lines that more closely resemble cognate tumour profiles than commonly used cell lines, and we propose these lines as the most suitable models of ovarian cancer. Our results indicate that the gap between cell lines and tumours can be bridged by genomically informed choices of cell line models for all tumour types.

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    • "To the aim of the study, we selected 4 different ovarian cancer cell lines among those indicated as really representative of HGSOC lesions[18,19]and evaluated the expression of hormone receptors by RT-PCR and WB analyses (Figure 1). MCF-7 cells were used as positive control. "
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    • "Differential gene expression analyses have identified differences , but not core similarities, between cell lines and tumors for particular cancers. Comparisons of cell lines and tumors on this basis are uninformative, as they simply separate in vivo and in vitro samples (Domcke et al., 2013). Supervised gene lists can be used to identify suitable tumor models from cancer cell lines (Dancik et al., 2011; Gillet et al., 2011; Uva et al., 2010), or similarities between cancer cell lines and their tumors of origin can be scored with a tissue similarity index (TSI). "
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    • "See also Figure S1. Cell 162, 974–986, August 27, 2015 ª2015 Elsevier Inc. 975 Domcke et al., 2013). Aza induced partial IRF7 demethylation and increased expression in this cell line at days 7 and 10 while carboplatin did not (Figures 1B, 1C, and S3A), and IRF7 knockdown significantly reduced the Aza interferon response (Figures S3B and S3C). "
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