Genetic and Epigenetic Mechanisms in Gastric Cancer

Gastric cancer (GC) is one of the deadliest malignancies worldwide. Complex disease heterogeneity, late diagnosis, and suboptimal therapies result in the poor prognosis of patients. Besides genetic alterations and environmental factors, it has been demonstrated that alterations of the epigenetic machinery guide cancer onset and progression, representing a hallmark of gastric malignancies. Moreover, epigenetic mechanisms undergo an intricate crosstalk, and distinct epigenomic profiles can be shaped under different microenvironmental contexts. In this scenario, targeting epigenetic mechanisms could be an interesting therapeutic strategy to overcome gastric cancer heterogeneity, and the efforts conducted to date are delivering promising results. In this review, we summarize the key epigenetic events involved in gastric cancer development. We conclude with a discussion of new promising epigenetic strategies for gastric cancer treatment.

Download Full-text

Epigenetic mechanisms in gastric cancer

Epigenomics ◽

10.2217/epi.12.22 ◽

2012 ◽

Vol 4 (3) ◽

pp. 279-294 ◽

Cited By ~ 69

Author(s):

Carolina Oliveira Gigek ◽

Elizabeth Suchi Chen ◽

Danielle Queiroz Calcagno ◽

Fernanda Wisnieski ◽

Rommel Rodriguez Burbano ◽

...

Keyword(s):

Gastric Cancer ◽

Epigenetic Mechanisms

Download Full-text

Somatic mutations in epigenetic regulation genes detected by NGS in gastric tumors

Nauchno-prakticheskii zhurnal «Medicinskaia genetika» ◽

10.25557/2073-7998.2020.06.75-76 ◽

2020 ◽

pp. 75-76

Author(s):

М.В. Немцова ◽

А.И. Калинкин ◽

Е.Б. Кузнецова ◽

Е.А. Алексеева ◽

И.В. Буре ◽

...

Keyword(s):

Gene Expression ◽

Gastric Cancer ◽

Epigenetic Regulation ◽

Somatic Mutations ◽

Prognostic Markers ◽

Epigenetic Mechanisms ◽

Clinical Marker ◽

Mutational Profiling ◽

Cell Life ◽

First Results

Эпигенетические механизмы регулируют структуру хроматина и создают устойчивые закономерности экспрессии генов в процессе жизни клеток. Нарушение эпигенетической регуляции играет значительную роль в канцерогенезе, инвазии, рецидивировании и метастазировании опухолей и может служить полезным клиническим маркером. Мутационное профилирование генов эпигенетической регуляции в опухолевых образцах рака желудка позволит определить новые клинические и прогностические маркеры и дополнительные таргеты для лечения пациентов. В статье представлены первые результаты исследования соматических мутаций в генах эпигенетической регуляции, проведенного методом NGS. Epigenetic mechanisms regulate chromatin structure and create stable patterns of gene expression during cell life. Violation of epigenetic regulation plays a significant role in carcinogenesis, invasion, recurrence and metastasis of tumors, and can serve as a useful clinical marker. Mutational profiling of epigenetic regulation genes in tumor samples of gastric cancer will allow us to identify new clinical and prognostic markers and additional targets for the treatment of patients with gastric cancer. This article presents the first results of a study of somatic mutations in the epigenetic regulation genes carried out using NGS.

Download Full-text

MicroRNA-31 Function as a Suppressor Was Regulated by Epigenetic Mechanisms in Gastric Cancer

BioMed Research International ◽

10.1155/2017/5348490 ◽

2017 ◽

Vol 2017 ◽

pp. 1-11 ◽

Cited By ~ 7

Author(s):

Jun Wei ◽

Zijian Wang ◽

Zhixiang Wang ◽

Yong Yang ◽

Changlai Fu ◽

...

Keyword(s):

Gastric Cancer ◽

Dna Methylation ◽

Cell Lines ◽

Methylation Status ◽

Ectopic Expression ◽

Luciferase Reporter ◽

Cancer Tissue ◽

Epigenetic Mechanisms ◽

Gastric Cancer Cells ◽

Aberrant Expression

Gastric cancer is one of the most lethal malignancies worldwide. The aberrant expression of microRNA-31 (miR-31) has been reported in gastric cancer; however, its regulation mechanisms are still unclear. Here, we confirmed that miR-31 expression was significantly decreased in gastric cancer tissue and cell lines. Ectopic expression of miR-31 potentially suppresses proliferation and induced early apoptosis in gastric cancer cells. Furthermore, miR-31 expression was regulated as a result of epigenetic mechanisms. The downregulation of miR-31 was associated with promoter DNA methylation status in gastric cancer and cell lines. Moreover, we found that HDAC2 was the direct target of miR-31 by binding to 3′-UTR from the results of luciferase reporter assays, qRT-PCR, and western blotting. HDAC2 played an activation role in tumor growth, whose expression is upregulated and inversely associated with miR-31 levels. All the results suggested that miR-31 function as a crucial tumor suppressor was regulated by epigenetic mechanisms in gastric cancer. We found an epigenetic pathway loop, DNA methylation-miRNA expression-target gene-tumor progression in gastric cancer, and also provided implications for molecular diagnosis and therapeutics of gastric malignancies by detecting miR-31 as a potential target.

Download Full-text

Ultrastructural Cytochemical Study of Human Gastric Cancer: Observation of AKP ase,ACP ase,G6P ase,TPP ase and CO ase

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158819 ◽

1990 ◽

Vol 48 (3) ◽

pp. 254-255

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Du Wei Dong ◽

Xu Ai Liam

Keyword(s):

Gastric Cancer ◽

Gastric Epithelium ◽

Human Gastric Cancer ◽

Electron Microscopic ◽

Cytochemical Study ◽

Electron Microscopic Cytochemistry ◽

Cytochemical Reaction ◽

Set Up ◽

Cancer Tissues ◽

Cytochemical Technique

The activities and distributions of AKPase ,ACPase,G6Pase,TPPase and COase in human normal gastric mucosa and gastric cancer tissues were studied histochemically at light microscopic level. These enzymes are the marker enzymes of cell membrane lysosome endoplasmic reticulum, Golgi apparatus and mitochondrion objectively. On the basis of the research we set up a special ultrastructural cytochemical technique and first researched into gastric cancer domesticly. Ultrastructural cytochemistry is also called electron microscopic cytochemistry. This new technique possesses both the sensitivity of cytochemical reaction andi the high resolution of electron microscope. It is characterized by direct observation,exact localization and the combination morphology with function.The distributions of AKPase,ACPase,G6Pase,TPPase and COase in 14 cases of gastric cancer and 1 case of gastric Denign lesion were studied ultrastructurally. The results showed: 1. normal gastric epithelium had no AKPase reaction. The reaction of ACPase,G6Pase,TPPase and Coase were found in the corresponding organella, which were consistent with their function.

Download Full-text

Ultrastructural Localization Study of Carcinoembryonic Antigen (CEA) in Gastric Cancer: Immunoelectron Microscopic Observation

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158807 ◽

1990 ◽

Vol 48 (3) ◽

pp. 252-253

Author(s):

Dong Yuming ◽

Yang Guanglin ◽

Wu Jifeng ◽

Chen Xiaolin

Keyword(s):

Gastric Cancer ◽

Intestinal Metaplasia ◽

Cancer Cells ◽

Microscopic Observation ◽

Biological Significance ◽

Ultrastructural Localization ◽

Mucinous Carcinoma ◽

Surface Glycoprotein ◽

Tubular Adenocarcinoma ◽

Pap Method

On the basis of light microscopic observation, the ultrastructural localization of CEA in gastric cancer was studied by immunoelectron microscopic technique. The distribution of CEA in gastric cancer and its biological significance and the mechanism of abnormal distribution of CEA were further discussed.Among 104 surgically resected specimens of gastric cancer with PAP method at light microscopic level, the incidence of CEA(+) was 85.58%. All of mucinous carcinoma exhibited CEA(+). In tubular adenocarcinoma the incidence of CEA(+) showed a tendency to rising with the increase of degree of differentiation. In normal epithelia and intestinal metaplasia CEA was faintly present and was found only in the luminal surface. The CEA staining patterns in cancer cells were of three types--- cytoplasmic, membranous and weak reactive type. The ultrastructural localization of CEA in 14 cases of gastric cancer was studied by immunoelectron microscopic technique.There was a little or no CEA in the microvilli of normal epithelia. In intestinal metaplasia CEA was found on the microvilli of absorptive cells and among the mucus particles of goblet cells. In gastric cancer CEA was also distributed on the lateral and basal surface or even over the entire surface of cancer cells and lost their polarity completely. Many studies had proved that the alterations in surface glycoprotein were characteristic changes of tumor cells. The antigenic determinant of CEA was glycoprotein, so the alterations of tumor-associated surface glycoprotein opened up a new way for the diagnosis of tumors.

Download Full-text