Abstract 5366: Mutation signature of TP53 gene in H. pylori-associated inflamed gastric mucosa during gastric carcinogenesis

2021 ◽

Vol 21 (4) ◽

pp. 256-266

Author(s):

Ji Min Choi ◽

Sang Gyun Kim

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Gastric Carcinogenesis ◽

Point Of View ◽

Epigenetic Changes ◽

Epigenetic Alterations ◽

Helicobacter Pylori Eradication ◽

Gastric Cancer Prevention ◽

H Pylori

It is known that gastric carcinogenesis results from the progressive changes from chronic gastritis to gastric atrophy, intestinal metaplasia, dysplasia, and invasive carcinoma. Several genetic and epigenetic alterations are involved in this process, and Helicobacter pylori (H. pylori) infection is believed to induce the initiation and progression of these steps. From an epigenetic point of view, H. pylori induces hypermethylation of genes involved in the development of gastric cancer and regulates the expression of various microRNAs (miRNAs). These H. pylori-related epigenetic changes are accumulated not only at the site of neoplasm but also in the adjacent non-cancerous gastric mucosa. Thereby, a state vulnerable to gastric cancer known as an epigenetic field defect is formed. H. pylori eradication can have an effective chemopreventive effect in gastric carcinogenesis. However, the molecular biological changes that occur in the stomach environment during H. pylori eradication have not yet been established. Several studies have reported that H. pylori eradication can restore infection-related changes, especially epigenetic alterations in gastric cancer-related genes, but some studies have shown otherwise. Simply put, it appears that the recovery of methylated gastric cancer-related genes and miRNAs during H. pylori eradication may vary among genes and may also differ depending on the histological subtype of the gastric mucosa. In this review, we will discuss the potential mechanism of gastric cancer prevention by H. pylori eradication, mainly from an epigenetic perspective.

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Analysis of the differences in structural chromosomal aberrations of the gastric mucosa between H. pylori positive and negative gastric cancer patients: Involvement of H. pylori in the onset of gastric cancer and examination of the mechanism in gastric carcinogenesis following H. pylori eradication

Oncology Reports ◽

10.3892/or.16.6.1333 ◽

2006 ◽

Author(s):

Tadashi Ohara ◽

Junji Kasanuki ◽

Hisaaki Ohara ◽

Yuhsaku Kanoh ◽

Hidekazu Suzuki ◽

...

Keyword(s):

Gastric Cancer ◽

Gastric Mucosa ◽

Cancer Patients ◽

Chromosomal Aberrations ◽

Gastric Carcinogenesis ◽

H Pylori ◽

Gastric Cancer Patients

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H. pylori down-regulates TRAIL (DR4)-receptors in the human gastric mucosa, a possible mechanism for chronic persistence

Gastroenterology ◽

10.1016/s0016-5085(01)80401-7 ◽

2001 ◽

Vol 120 (5) ◽

pp. A81-A81

Author(s):

B NEU ◽

R RAD ◽

M NEUHOFER ◽

C TRAUTWEIN ◽

M GERHARD ◽

...

Keyword(s):

Gastric Mucosa ◽

Human Gastric Mucosa ◽

H Pylori

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Genetic Characterization and Clinical Features of Helicobacter pylori Negative Gastric Mucosa-Associated Lymphoid Tissue Lymphoma

Cancers ◽

10.3390/cancers13122993 ◽

2021 ◽

Vol 13 (12) ◽

pp. 2993

Author(s):

Barbara Kiesewetter ◽

Christiane Copie-Bergman ◽

Michael Levy ◽

Fangtian Wu ◽

Jehan Dupuis ◽

...

Keyword(s):

Gastric Mucosa ◽

Signaling Pathways ◽

Clinical Features ◽

Malt Lymphoma ◽

Lymphoid Tissue ◽

Targeted Sequencing ◽

Clinicopathological Parameters ◽

Gastric Malt Lymphoma ◽

Genetic Changes ◽

H Pylori

Background: In Western countries, the prevalence of gastric mucosa-associated lymphoid tissue (MALT) lymphoma has declined over the last three decades. Contemporaneously, H. pylori negative gastric MALT lymphoma is increasingly encountered, and their genetic basis and clinical features remain elusive. Methods: A total of 57 cases of H. pylori negative gastric MALT lymphoma were reviewed and investigated for chromosome translocation by fluorescence in-situ hybridization and for somatic mutations by the targeted sequencing of 93 genes. Results: MALT1 translocation, most likely t(11;18)(q21;q21)/BIRC3-MALT1, was detected in 39% (22/57) cases, and IGH translocation was further seen in 12 MALT1-negative cases, together accounting for 60% of the cohort. Targeted sequencing was successful in 35 cases, and showed frequent mutations in NF-κB signaling pathways (TNFAIP3 = 23%, CARD11 = 9%, MAP3K14 = 9%), together affecting 14 cases (40%). The NF-κB pathway mutations were mutually exclusive from MALT1, albeit not IGH translocation, altogether occurring in 86% of cases. There was no significant correlation between the genetic changes and clinicopathological parameters. The patients showed a median of progression-free survival (PFS) of 66.3 months, and a significant superior PFS when treated with systemic versus antibiotic therapy (p = 0.004). Conclusion: H. pylori negative gastric MALT lymphoma is characterized by highly frequent genetic changes in the NF-κB signaling pathways.

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Gastric Cancer Microbiome

Pathobiology ◽

10.1159/000512833 ◽

2021 ◽

Vol 88 (2) ◽

pp. 156-169

Author(s):

Williams Fernandes Barra ◽

Dionison Pereira Sarquis ◽

André Salim Khayat ◽

Bruna Cláudia Meireles Khayat ◽

Samia Demachki ◽

...

Keyword(s):

Gastric Cancer ◽

Small Sample Size ◽

Total Sample ◽

Clinical Situation ◽

Gastric Carcinogenesis ◽

Comprehensive Analysis ◽

Small Sample ◽

Metagenomic Data ◽

Clinical Scenarios ◽

H Pylori

Identifying a microbiome pattern in gastric cancer (GC) is hugely debatable due to the variation resulting from the diversity of the studied populations, clinical scenarios, and metagenomic approach. H. pylori remains the main microorganism impacting gastric carcinogenesis and seems necessary for the initial steps of the process. Nevertheless, an additional non-H. pylori microbiome pattern is also described, mainly at the final steps of the carcinogenesis. Unfortunately, most of the presented results are not reproducible, and there are no consensual candidates to share the H. pylori protagonists. Limitations to reach a consistent interpretation of metagenomic data include contamination along every step of the process, which might cause relevant misinterpretations. In addition, the functional consequences of an altered microbiome might be addressed. Aiming to minimize methodological bias and limitations due to small sample size and the lack of standardization of bioinformatics assessment and interpretation, we carried out a comprehensive analysis of the publicly available metagenomic data from various conditions relevant to gastric carcinogenesis. Mainly, instead of just analyzing the results of each available publication, a new approach was launched, allowing the comprehensive analysis of the total sample amount, aiming to produce a reliable interpretation due to using a significant number of samples, from different origins, in a standard protocol. Among the main results, Helicobacter and Prevotella figured in the “top 6” genera of every group. Helicobacter was the first one in chronic gastritis (CG), gastric cancer (GC), and adjacent (ADJ) groups, while Prevotella was the leader among healthy control (HC) samples. Groups of bacteria are differently abundant in each clinical situation, and bacterial metabolic pathways also diverge along the carcinogenesis cascade. This information may support future microbiome interventions aiming to face the carcinogenesis process and/or reduce GC risk.

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Helicobacter pylori Virulence Factors—Mechanisms of Bacterial Pathogenicity in the Gastric Microenvironment

Cells ◽

10.3390/cells10010027 ◽

2020 ◽

Vol 10 (1) ◽

pp. 27

Author(s):

Jacek Baj ◽

Alicja Forma ◽

Monika Sitarz ◽

Piero Portincasa ◽

Gabriella Garruti ◽

...

Keyword(s):

Gastric Cancer ◽

Helicobacter Pylori ◽

Gastric Mucosa ◽

Virulence Factors ◽

Premalignant Lesions ◽

Bacterial Pathogenicity ◽

Current State ◽

Genetic And Environmental Factors ◽

H Pylori ◽

Stimulation Of

Gastric cancer constitutes one of the most prevalent malignancies in both sexes; it is currently the fourth major cause of cancer-related deaths worldwide. The pathogenesis of gastric cancer is associated with the interaction between genetic and environmental factors, among which infection by Helicobacter pylori (H. pylori) is of major importance. The invasion, survival, colonization, and stimulation of further inflammation within the gastric mucosa are possible due to several evasive mechanisms induced by the virulence factors that are expressed by the bacterium. The knowledge concerning the mechanisms of H. pylori pathogenicity is crucial to ameliorate eradication strategies preventing the possible induction of carcinogenesis. This review highlights the current state of knowledge and the most recent findings regarding H. pylori virulence factors and their relationship with gastric premalignant lesions and further carcinogenesis.

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