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

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.

Far Upstream Element-Binding Protein 1 (FUBP1) is Overexpressed in Human Gastric Cancer Tissue Compared to Non-Cancerous Tissue

“…In contrast, Japan is a country in which detection takes place early, with a very high incidence of gastric cancer reporting 5-year survival rates of 90% [19]. The development and progression of gastric cancer is a slow process of evolution that involves multiple genetic alterations [20]. Exploring the genes and proteins of such premalignant lesions could lead to better comprehension of their pathogenesis, and thus to the early detection of patients with disease progression, with intervention aimed at cancer prevention and improved patient survival.…”

Los receptores epidérmicos humanos en el cáncer gástrico: alteraciones moleculares y su papel como diana terapéutica

“…HER3 está sobreexpresado en el 87% de los tumores gástricos 15 , y es más común en el citoplasma (64%) que en el núcleo (34%) o la membrana (2%) 6,7 , aunque Choi, et al 15 observaron que HER3 se encuentra principalmente en el núcleo. Para algunos autores, la sobreexpresión de HER3 se relaciona con el subtipo intestinal de CG 6,7,16 , mientras que para otros se relaciona con el subtipo difuso 17 . Por otra parte, también se ha descrito la falta de asociación con algún subtipo de CG 18,19 .…”

Epigenetic Biomarkers for the Early Detection of Gastrointestinal Cancer

“…DNA methylation mapping also shows that the highest CGI hypermethylation frequency takes place in GC [9,10]. For instance, HOP homeobox methylation has shown potential as a biomarker with 84% of hypermethylated samples versus 10% of matched adjacent normal tissues [11].…”