Organ-specific profiles of genetic changes in cancers caused by activation-induced cytidine deaminase expression
Toshiyuki Morisawa
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorCorresponding Author
Hiroyuki Marusawa
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Fax: +81-75-751-4303.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kawara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, JapanSearch for more papers by this authorYoshihide Ueda
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorAkio Iwai
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorIl-mi Okazaki
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorTasuku Honjo
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorTsutomu Chiba
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorToshiyuki Morisawa
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorCorresponding Author
Hiroyuki Marusawa
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Fax: +81-75-751-4303.
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kawara-Cho, Shogoin, Sakyo-Ku, Kyoto 606-8507, JapanSearch for more papers by this authorYoshihide Ueda
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorAkio Iwai
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorIl-mi Okazaki
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorTasuku Honjo
Department of Immunology and Genomic Medicine, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorTsutomu Chiba
Department of Gastroenterology and Hepatology, Graduate School of Medicine, Kyoto University, Kyoto, Japan
Search for more papers by this authorAbstract
Various molecular changes characterizing organ-specific carcinogenesis have been identified in human tumors; however, the molecular mechanisms of the genomic changes specific for each cancer are not well defined. A transgenic (Tg) mouse model with constitutive expression of the nucleotide-editing enzyme, activation-induced cytidine deaminase (AID), develops tumors in various organs as a result of the mutagenic activities of AID. This phenotypic character of AID Tg mice allowed us to analyze the organ-specific genetic changes in tumor-related genes commonly triggered by AID-mediated mutagenesis. Among the 80 AID Tg mice analyzed, 11 mice developed hepatocellular carcinomas, and 7 developed lung cancers. In addition, 1 developed the gastric cancer and 3 developed gastric adenomas. Organ-specific preferences for nucleotide changes were observed in some of the tumor-related genes in each epithelial tissue of the AID Tg mice. Of note, the c-myc and K-ras genes were the preferential targets of the mutagenic activity of AID in lung and stomach cancers, respectively, whereas mutations in the p53 and β-catenin genes were commonly observed in all 3 organs. Quantitative RT-PCR analyses revealed that alpha-fetoprotein, insulin-like growth factor2 and cyclin D1 genes were specifically upregulated in HCC, whereas upregulation of the matrix metalloproteinase7 gene was more marked in lung cancer. Our findings suggest that AID, a DNA mutator that plays a critical role linking inflammation to human cancers, might be involved in the generation of organ-specific genetic diversity in oncogenic pathways during cancer development. © 2008 Wiley-Liss, Inc.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
| Filename | Description |
|---|---|
| IJC_23853_sm_suppinfoTable1.doc26.5 KB | Supporting information Table 1. Oligonucleotide primers for the amplification of DNA sequence used in the current study |
| IJC_23853_sm_suppinfoTable2.doc28 KB | Supporting information Table 2. Oligonucleotide primers for the amplification of RNA sequence used in the current study |
Please note: The publisher is not responsible for the content or functionality of any supporting information supplied by the authors. Any queries (other than missing content) should be directed to the corresponding author for the article.
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