title: Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma.
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.
authors.affiliation: TRON gGmbH - Translational Oncology, Johannes Gutenberg-University Medical Center gGmbH, Langenbeckstr, 1, Building 708, 55131 Mainz, Germany. john.castle@tron-mainz.de.
authors.forename: John C
authors.initials: JC
authors.lastname: Castle
authors.forename: Martin
authors.initials: M
authors.lastname: Loewer
authors.forename: Sebastian
authors.initials: S
authors.lastname: Boegel
authors.forename: Jos
authors.initials: J
authors.lastname: de Graaf
authors.forename: Christian
authors.initials: C
authors.lastname: Bender
authors.forename: Arbel D
authors.initials: AD
authors.lastname: Tadmor
authors.forename: Valesca
authors.initials: V
authors.lastname: Boisguerin
authors.forename: Thomas
authors.initials: T
authors.lastname: Bukur
authors.forename: Patrick
authors.initials: P
authors.lastname: Sorn
authors.forename: Claudia
authors.initials: C
authors.lastname: Paret
authors.forename: Mustafa
authors.initials: M
authors.lastname: Diken
authors.forename: Sebastian
authors.initials: S
authors.lastname: Kreiter
authors.forename: Özlem
authors.initials: Ö
authors.lastname: Türeci
authors.forename: Ugur
authors.initials: U
authors.lastname: Sahin
mesh_terms: D000818:Animals; D000951:Antigens, Neoplasm / Q000235:genetics / Q000378:metabolism; D002277:Carcinoma / Q000235:genetics* / Q000276:immunology; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000235:genetics* / Q000276:immunology; D019941:Cyclin-Dependent Kinase Inhibitor p16 / Q000235:genetics / Q000378:metabolism; D059014:High-Throughput Nucleotide Sequencing; D051379:Mice; D008807:Mice, Inbred BALB C; D020641:Polymorphism, Single Nucleotide; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics; D017422:Sequence Analysis, DNA; D059467:Transcriptome
chemical_list: D000951:Antigens, Neoplasm; D019941:Cyclin-Dependent Kinase Inhibitor p16; C495971:Hras protein, mouse; D016283:Proto-Oncogene Proteins p21(ras)