Mutation and expression analysis of the IDH1, IDH2, DNMT3A, and MYD88 genes in colorectal cancer |
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Authors: | Wen-Liang Li Mei-Sheng Xiao Deng-Feng Zhang Dandan Yu Run-Xiang Yang Xiao-Yan Li Yong-Gang Yao |
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Institution: | 1. Department of Oncology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China;2. Key Laboratory of Animal Models and Human Disease Mechanisms of the Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, Kunming, Yunnan 650223, China;3. Chemotherapy Research Center, Yunnan Provincial Tumor Hospital, Kunming Medical University, Kunming, China;4. Department of Gastroenterology, The First Affiliated Hospital of Kunming Medical University, Kunming, Yunnan 650032, China;5. Kunming College of Life Science, University of Chinese Academy of Sciences, Kunming, Yunnan 650204, China |
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Abstract: | Colorectal cancer (CRC) is one of the leading causes of death around the world. Its genetic mechanism was intensively investigated in the past decades with findings of a number of canonical oncogenes and tumor-suppressor genes such as APC, KRAS, and TP53. Recent genome-wide association and sequencing studies have identified a series of promising oncogenes including IDH1, IDH2, DNMT3A, and MYD88 in hematologic malignancies. However, whether these genes are involved in CRC remains unknown. In this study, we screened the hotspot mutations of these four genes in 305 CRC samples from Han Chinese by direct sequencing. mRNA expression levels of these genes were quantified by quantitative real-time PCR (RT-qPCR) in paired cancerous and paracancerous tissues. Association analyses between mRNA expression levels and different cancerous stages were performed. Except for one patient harboring IDH1 mutation p.I99M, we identified no previously reported hotspot mutations in colorectal cancer tissues. mRNA expression levels of IDH1, DNMT3A, and MYD88, but not IDH2, were significantly decreased in the cancerous tissues comparing with the paired paracancerous normal tissues. Taken together, the hotspot mutations of IDH1, IDH2, DNMT3A, and MYD88 gene were absent in CRC. Aberrant mRNA expression of IDH1, DNMT3A, and MYD88 gene might be actively involved in the development of CRC. |
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Keywords: | CRC colorectal cancer APC adenomatous polyposis coli KRAS Kirsten rat sarcoma viral oncogene homolog TP53 tumor protein p53 IDH1 isocitrate dehydrogenase 1 (NADP +) soluble IDH2 isocitrate dehydrogenase 2 (NADP +) mitochondrial DNMT3A DNA (cytosine-5-)-methyltransferase 3 alpha MYD88 myeloid differentiation primary response 88 UC ulcerative colitis FAP familial adenomatous polyposis HNPCC hereditary nonpolyposis cancer EGFR epidermal growth factor receptor BRAF v-raf murine sarcoma viral oncogene homolog B SF3B1 splicing factor 3b subunit 1 MAP2K1/2 mitogen-activated protein kinase kinase 1/2 2-HG 2-hydroxyglutarate AML acute myeloid leukemia TLR Toll-like receptor IL-1R interleukin 1 receptor NF-κB nuclear factor-kappa B RT-qPCR real-time quantitative PCR GAPDH glyceraldehyde 3-phosphate dehydrogenase DSS dextran sodium sulfate α-KG α-ketoglutarate HepG2 human hepatocellular liver carcinoma cell line HIF-1α hypoxia-inducible factor 1-α GLUT1 glucose transporter 1 VEGF vascular endothelial growth factor HOXA2 homeobox A2 HOXA4 homeobox A4 HOXA6 homeobox A4 WT wild-type |
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