Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection

Wu, Ming–Shiang; Shun, Chia‐Tung; Wang, Hsiu-Po; Sheu, Jin‐Chuan; Lee, Wei-Jei; Wang, Teh‐Hong; Lin, Jaw–Town

doi:10.1016/s0016-5085(97)70071-4

Cited by 135 publications

(104 citation statements)

References 28 publications

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“…The tumorigenesis process of gastric cancer has been widely studied. Besides environmental factors (Chyou et al, 1990;Nomura et al, 1990;Parsonnet et al, 1991;Tsugane and Sasazuki, 2007;Suzuki et al, 2009;Polk and Peek, 2010), genetic alterations of oncogenes, tumor-suppressor genes, cell cycle regulators, cell adhesion molecules and DNA repair genes have been identified to contribute to development or progression of gastric cancer (Wu et al, 1997;Zheng et al, 2004;Stock and Otto, 2005). The gene instability in gastric cancer including gene amplification, loss of heterozygosity (Sano et al, 1991) or microsatellite instability (Fang et al, 2003) may cause the inactivation of some tumor-suppressor genes, such as p53, and deregulation of some signaling molecules so as to enhance some signaling pathways, such as Wnt or Ras-dependent mitogen-activated protein kinase (MAPK) pathway, which may promote the tumorigenesis (Kim et al, 1991;Clements et al, 2002;Stock and Otto, 2005).…”

Section: Introductionmentioning

confidence: 99%

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

et al. 2012

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Activation of Akt signaling pathway has been suggested involving in chemoresistance, metastasis and tumorigenesis of gastric cancer. However, the mechanism of Akt regulation in gastric cancer is not fully understood. RUNX3, which was first identified as a transcription factor, suppresses gastric tumorigenesis through regulating expression of target genes. Here, we found that restoration of RUNX3 significantly downregulates the protein and mRNA expression of Akt1 in gastric cancer cell lines, AGS and SNU-1. Knockdown of RUNX3 upregulates protein and mRNA expression of Akt1 in normal gastric epithelial cell line, GES-1. The negative correlation of RUNX3 and Akt expression and downstream b-catenin/cyclin D1 effectors was further confirmed in AGS and GES-1 cell lines, as well as clinical specimens of gastric cancer. We identified two RUNX3-binding sites in Akt1 promoter and the binding of RUNX3 on Akt1 promoter significantly inhibits Akt1 expression. The RUNX3-mediated inhibition of Akt1 caused b-catenin protein degradation and then cyclin D1 downregulation. Restoration of cyclin D1 reverses cell growth inhibition and G1 phase arrest induced by RUNX3 in gastric cancer cells. Our results show that loss of RUNX3 expression can enhance the Akt1-mediated signaling pathway and promote the tumorigenesis process in human gastric cancer.

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Section: Introductionmentioning

confidence: 99%

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

et al. 2012

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“…Analysis of chromosomal imbalances by chromosome CGH has greatly contributed to the current knowledge of genomic alterations associated with gastric cancer and several chromosomal regions with frequent gains or losses have been identified (Koizumi et al, 1997;Kokkola et al, 1997;Wu et al, 1997;Koo et al, 2000;Grieken van et al, 2000;Hausen zur et al, 2001). However, the information obtained is limited to a resolution of approximately 3-10 Mb.…”

Section: Introductionmentioning

confidence: 99%

Genomic profiling of gastric cancer predicts lymph node status and survival

et al. 2003

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Gastric carcinogenesis is driven by an accumulation of genetic changes that to a large extent occur at the chromosomal level. We analysed the patterns of chromosomal instability in 35 gastric carcinomas and their clinical correlations. With microarray competitive genomic hybridization, genomewide chromosomal copy number changes can be studied with high resolution and sensitivity. A genomewide scanning array with 2275 BAC and P1 clones spotted in triplicate was used. This array provided an average resolution of 1.4 Mb across the genome. Patterns of chromosomal aberrations were analysed by hierarchical cluster analysis of the normalized log 2 tumour to normal fluorescence ratios of all clones, and cluster membership was correlated to clinicopathological data including survival. Hierarchical cluster analysis revealed three groups with different genomic profiles that correlated significantly with lymph node status (P ¼ 0.02). Moreover, gastric cancer cases from cluster 3 showed a significantly better prognosis than those from clusters 1 and 2 (P ¼ 0.02). Genomic profiling of gastric adenocarcinomas based on microarray analysis of chromosomal copy number changes predicted lymph node status and survival. The possibility to discriminate between patients with a high risk of lymph node metastasis could clinically be helpful for selecting patients for extended lymph node resection.

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“…The intestinal type is strongly associated with Helicobacter pylori, and usually arises on a backdrop of chronic gastritis, gastric atrophy, and intestinal metaplasia (Munoz, Matko, et al, 1972) In contrast, poorly differentiated adenocarcinomas are usually not associated with these changes. In addition, it has been noted that LOH of APC is more common in intestinal-type gastric cancer irrespective of the stage, but occurs rarely in diffuse-type gastric cancer; in contrast LOH ofDCC occurs primarily in advanced intestinal-type gastric cancer and infrequently in early gastric cancer or advanced diffuse-type gastric cancer (Wu, Shun, et al, 1997).…”

Section: Okamoto Et Al Have Reported the Data Of A Single Institute mentioning

confidence: 99%

Clinicopathological Time Trends of 2569 Gastric Carcinomas in Japan During the Past 20 Years

Ogoshi

Isono

2003

ACRT

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men. Analysis revealed that there were no significant differences in the conditions of lymph node metastasis, and also no significant differences in the frequencies of tumor depth, gender, and double cancer between A and B groups. With regard to differences in age (less than 49 years vs. 50 years and over), there was a significant increase in the incidence of cancer in the patients 50 years and over. The pattern of tumor location of the lower third of the stomach increased over the period of the study, while that of the upper third of the stomach decreased. With regard to histological type, there was a significant increase in the incidence of a moderately differentiated type of tubular adenocarcinoma and poorly differentiated adenocarcinoma (por), but a significant decrease in that of signet ring cell carcinoma. Taking every factor into consideration, the incidence of early-localized cancers appears to have increased and that of advanced invasive cancers appears to have decreased in Japan during the past 20 years.In conclusion, adenocarcinomas of the stomach with intestinal types, which related with the HP infection, decreased and those of diffuse types, which did not relate with the HP infection increased during the past 20 years.

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Genetic alterations in gastric cancer: relation to histological subtypes, tumor stage, and Helicobacter pylori infection

Cited by 135 publications

References 28 publications

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

RUNX3-mediated transcriptional inhibition of Akt suppresses tumorigenesis of human gastric cancer cells

Genomic profiling of gastric cancer predicts lymph node status and survival

Clinicopathological Time Trends of 2569 Gastric Carcinomas in Japan During the Past 20 Years

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