Pan-cancer analysis of DNA epigenetic modifications by hydrophilic interaction liquid chromatography-tandem mass spectrometry |
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| Institution: | 1. Cancer Institute (Key Laboratory of Cancer Prevention and Intervention, China National Ministry of Education), The Second Affiliated Hospital, Zhejiang University School of Medicine, Hangzhou 310009, China;2. Cancer Center, Zhejiang University, Hangzhou 310058, China;1. Department of Chemistry, Jinan University, Guangzhou 510632, China;2. Department of Orthopedics, Affiliated Hospital of Guangdong Medical University, Zhanjiang 524001, China;1. Department of Dermatology, the Second Hospital Affiliated to Xi''an Jiaotong University, Xi''an 710061, China;2. School of Chemical Engineering and Technology, Xi''an Jiaotong University, Xi''an 710049, China;3. Infectious Disease Department, the Second Xiangya Hospital of Central South University, Changsha 410011, China;4. Pooling Medical Research Institutes, Hangzhou 310053, China;5. Department of Pharmacy, Shaanxi Provincial People''s Hospital, Xi''an 710068, China;1. State Key Laboratory of Organic Electronics and Information Displays & Jiangsu Key Laboratory for Biosensors, Institute of Advanced Materials (IAM), Nanjing University of Posts and Telecommunications, Nanjing 210023, China;2. School of Mechanical Engineering, Nanjing University of Science and Technology, Nanjing 210094, China;1. School of Chemistry, Sun Yat-Sen University, Guangzhou 510275, China;2. Key Laboratory of Tobacco Flavor Basic Research, Zhengzhou Tobacco Research Institute of CNTC, Zhengzhou 450001, China;1. Key Laboratory for Green Chemical Technology of Ministry of Education, School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, China;2. Haihe Laboratory of Sustainable Chemical Transformations, Tianjin 300192, China;3. Joint School of National University of Singapore and Tianjin University, International Campus of Tianjin University, Fuzhou 350207, China;4. Tianjin Key Laboratory of Molecular Optoelectronic Science, School of Science, Tianjin University, Tianjin 300072, China |
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| Abstract: | Accumulating evidence in recent years indicates that DNA methylation (5-methyl-2′-deoxycytidine, 5-mdC) and hydroxymethylation (5-hydroxymethyl-2′-deoxycytidine, 5-hmdC) have been implicated in various biological processes, and the aberrations of these DNA cytosine modifications is tightly associated with cancer. N6-methyl-2′-deoxyadenosine (m6dA), as a newly discovered epigenetic modification in genome of mammals, has been demonstrated to play vital regulatory roles in tumorigenesis. However, the content information of m6dA in human tumor tissues is still limited and pan-cancer analysis of these DNA epigenetic modifications is lacked. Herein, we developed a sensitive and robust stable isotope-diluted hydrophilic interaction liquid chromatography-tandem mass spectrometry (HILIC-MS/MS) method for accurate quantification of m6dA, 5-mdC and 5-hmdC in genomic DNA from 82 pairs of human tumor tissues and matched tumor-adjacent normal tissues. The types of tumors included esophagus cancer, lung cancer, breast cancer, liver cancer, pancreatic cancer, gastric cancer, stromal tumor and colorectal cancer. Compared to the normal tissues, we revealed the level of m6dA was increased in tumor tissues of esophagus cancer, lung cancer and liver cancer, whereas the level of m6dA was diminished in tumor tissues of pancreatic cancer and gastric cancer; while the contents of 5-mdC and 5-hmdC exhibited significant decrease in tumor tissues of most types of cancer. It is worth noting that we revealed, for the first time, the content of genomic m6dA in pancreatic cancer, stromal tumor and colorectal cancer. The significant changes of these DNA epigenetic modifications indicate they may serve as indicators of cancers. In addition, this study will benefit for better understanding of the regulatory roles of these DNA epigenetic modifications in cancers. |
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