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Open Access Highly Accessed Research article

Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma

John C Castle1*, Martin Loewer1, Sebastian Boegel12, Jos de Graaf1, Christian Bender1, Arbel D Tadmor1, Valesca Boisguerin13, Thomas Bukur1, Patrick Sorn1, Claudia Paret1, Mustafa Diken1, Sebastian Kreiter1, Özlem Türeci2 and Ugur Sahin123*

Author Affiliations

1 TRON gGmbH - Translational Oncology, Johannes Gutenberg-University Medical Center gGmbH, Langenbeckstr. 1, Building 708, 55131 Mainz, Germany

2 University Medical Center of the Johannes Gutenberg-University Mainz, 55131 Mainz, Germany

3 BioNTech AG, Kupferbergterrasse 17-19, 55131 Mainz, Germany

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BMC Genomics 2014, 15:190  doi:10.1186/1471-2164-15-190

Published: 13 March 2014

Abstract

Background

Tumor models are critical for our understanding of cancer and the development of cancer therapeutics. Here, we present an integrated map of the genome, transcriptome and immunome of an epithelial mouse tumor, the CT26 colon carcinoma cell line.

Results

We found that Kras is homozygously mutated at p.G12D, Apc and Tp53 are not mutated, and Cdkn2a is homozygously deleted. Proliferation and stem-cell markers, including Top2a, Birc5 (Survivin), Cldn6 and Mki67, are highly expressed while differentiation and top-crypt markers Muc2, Ms4a8a (MS4A8B) and Epcam are not. Myc, Trp53 (tp53), Mdm2, Hif1a, and Nras are highly expressed while Egfr and Flt1 are not. MHC class I but not MHC class II is expressed. Several known cancer-testis antigens are expressed, including Atad2, Cep55, and Pbk. The highest expressed gene is a mutated form of the mouse tumor antigen gp70. Of the 1,688 non-synonymous point variations, 154 are both in expressed genes and in peptides predicted to bind MHC and thus potential targets for immunotherapy development. Based on its molecular signature, we predicted that CT26 is refractory to anti-EGFR mAbs and sensitive to MEK and MET inhibitors, as have been previously reported.

Conclusions

CT26 cells share molecular features with aggressive, undifferentiated, refractory human colorectal carcinoma cells. As CT26 is one of the most extensively used syngeneic mouse tumor models, our data provide a map for the rationale design of mode-of-action studies for pre-clinical evaluation of targeted- and immunotherapies.

Keywords:
Immunotherapy; Cancer models; Computational immunology; Colorectal cancer