Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma.
Immunomic, genomic and transcriptomic characterization of CT26 colorectal carcinoma.
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DOI：
10.1186/1471-2164-15-190
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发表时间：
2014-03-13
期刊：
影响因子：
4.4
通讯作者：
Sahin U
中科院分区：
文献类型：
--
作者：
Castle JC;Loewer M;Boegel S;de Graaf J;Bender C;Tadmor AD;Boisguerin V;Bukur T;Sorn P;Paret C;Diken M;Kreiter S;Türeci Ö;Sahin U
肿瘤模型对于我们理解癌症和癌症治疗的发展至关重要。在这里，我们展示了小鼠上皮肿瘤CT 26结肠癌细胞系的基因组、转录组和免疫组的综合图谱。我们发现Kras在p.G12D处同源突变，Apc和Tp 53没有突变，Cdkn 2a同源缺失。增殖和干细胞标志物，包括Top 2a，Birc 5（生存素），Cldn 6和Mki 67，高度表达，而分化和顶隐窝标志物Muc 2，Ms 4a 8a（MS 4A 8B）和Epcam没有。Myc、Trp 53（tp 53）、Mdm 2、Hif 1a和Nras高度表达，而Egfr和Flt 1不表达。表达MHC I类，但不表达MHC II类。表达了几种已知的癌症-睾丸抗原，包括Atad 2、Cep 55和Pbk。最高表达的基因是小鼠肿瘤抗原gp 70的突变形式。在1，688个非同义点变异中，154个既存在于表达的基因中，也存在于预测结合MHC的肽中，因此是免疫疗法开发的潜在靶点。基于其分子特征，我们预测CT 26对抗EGFR单克隆抗体是难治的，并且对MEK和MET抑制剂是敏感的，如先前所报道的。CT 26细胞与侵袭性、未分化、难治性人结直肠癌细胞具有共同的分子特征。由于CT 26是最广泛使用的同基因小鼠肿瘤模型之一，我们的数据为靶向和免疫治疗的临床前评价的作用模式研究的基本原理设计提供了一个地图。本文的在线版本（doi：10.1186/1471-2164-15-190）包含补充材料，可供授权用户使用。
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. 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. 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. The online version of this article (doi:10.1186/1471-2164-15-190) contains supplementary material, which is available to authorized users.
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