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Genomic and epigenetic profiles of gastric cancer: Potential diagnostic and therapeutic applications

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Abstract

Knowledge about the molecular profile of tumor tissues is crucial to effectively target cancer cells, because cancer is a genetic disease that involves multiple genetic and epigenetic alterations. Prominent aberrations include gene mutation, amplification, loss or deletion, as well as epigenetic alterations of the promoter DNA CpG islands. All of these aberrations can lead to dynamic changes in cancer cells, as demonstrated using resected tumor samples. There are two distinct pathological types of gastric cancer: the diffuse type and the intestinal type of gastric cancer. Diffuse type gastric cancer harbors aberrations in the FGFR2/ErbB3/PI3 kinase pathway, while intestinal type gastric cancer has an activated ErbB2 oncogenic pathway. On the other hand, the prometastatic oncogene PRL-3 is commonly activated in both types of advanced gastric cancer, and might represent a relevant therapeutic target for gastric cancer with lymph node metastasis or peritoneal dissemination. Numerous tumor suppressor genes can inhibit such oncogenic pathways, and DNA methylation in CpG islands of gene promoters is frequently found to suppress the expression of such genes in gastric cancer. Helicobacter pylori infection in normal gastric mucosa may cause p53 mutations through activation of activation-induced cytidine deaminase (AID) and/or promoter DNA methylation of E-cadherin, an initiator of gastric cancer, and such abnormalities are found even in the precancerous stage of gastric carcinogenesis. In addition, it has been demonstrated that there are highly relevant methylation genes involved in cancer (HRMGs) that exhibit very frequent cancer-specific methylation in gastric cancer. Such genes are potential targets for cancer treatment, and might also serve as biomarkers of gastric cancer for either the diagnosis or for determining the prognosis or the response to treatment.

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  1. Department of Surgery, Kitasato University School of Medicine, 1-15-1 Kitasato, Minami-ku, Sagamihara, Kanagawa, 252-0374, Japan

    Keishi Yamashita, Shinichi Sakuramoto & Masahiko Watanabe

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Yamashita, K., Sakuramoto, S. & Watanabe, M. Genomic and epigenetic profiles of gastric cancer: Potential diagnostic and therapeutic applications. Surg Today 41, 24–38 (2011). https://doi.org/10.1007/s00595-010-4370-5

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