Microsatellite alterations and target gene mutations in the early stages of multiple gastric cancer

2001 ◽  
Vol 194 (3) ◽  
pp. 334-340 ◽  
Author(s):  
Shin-ya Ogata ◽  
Gen Tamura ◽  
Yasushi Endoh ◽  
Ken Sakata ◽  
Kiyonari Ohmura ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Target Gene ◽  
Gene Mutations ◽  
Early Stages ◽  
Multiple Gastric Cancer

Gastric cancer with high-level microsatellite instability: target gene mutations, clinicopathologic features, and long-term survival

2008 ◽  
Vol 39 (6) ◽  
pp. 925-932 ◽  
Author(s):  
Mario Falchetti ◽  
Calogero Saieva ◽  
Ramona Lupi ◽  
Giovanna Masala ◽  
Piera Rizzolo ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Microsatellite Instability ◽  
Target Gene ◽  
Gene Mutations ◽  
Clinicopathologic Features ◽  
Term Survival ◽  
Long Term Survival ◽  
High Level

scholarly journals miR-335-5p Suppresses Gastric Cancer Progression by Targeting MAPK10

2020 ◽  
Author(s):  
Yi Gao ◽  
Yanfeng Wang ◽  
Xiaofei Wang ◽  
Changan Zhao ◽  
Fenghui Wang ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Cell Cycle ◽  
Cancer Cells ◽  
Cell Lines ◽  
Cancer Progression ◽  
Target Gene ◽  
Luciferase Reporter ◽  
Gastric Cancer Cells ◽  
Aberrant Expression ◽  
Related Target

Abstract Background: In recent years, many microRNAs(miRNAs) involved in cancer progression. The aberrant expression of miR-335-5p in tumorigenesis has been demonstrated. The present study aimed to investigate the molecular mechanisms underlying miR-335-5p- regulated MAPK10 expression in human gastric cancer（GC）.Methods: The quantitative real-time PCR was used to study the level of miR-335-5p expression in gastric cancer cell lines and tissues. Subsequently, the MTT and cloning formation assays were used to detect cell proliferation, while transwell and wound-healing assays were used to identify invasion and migration of the gastric cancer cells. The correlation between the miR-335-5p and the cell cycle-related target gene mitogen‑activated protein kinase 10 (MAPK10) in gastric cancer was analyzed based on the website. In addition, the target gene of miR-335-5p was detected by luciferase reporter assay, qRT-PCR, and western blotting.Results: The miR-335-5p level was down-regulated in GC tissues and cell lines. Furthermore, miR-335-5p inhibited proliferation, migration of gastric cancer cells, and induced apoptosis. During the G1/S phase, miR-335-5p arrested the cycle of gastric cancer cells in vitro. The correlation between the miR-335-5p and the cell cycle-related target gene MAPK10 in GC was analyzed, MAPK10 was directly targeted by the miR-335-5p.Conclusion: These data suggested that miR-335-5p acts as a tumor suppressor, and go through the MAPK10 to inhibit the GC progression.

scholarly journals Simultaneous detection of expression and gene mutations of HER2/neu in Chinese patients with gastric cancer

2010 ◽  
Vol 1 (3) ◽  
pp. 559-563 ◽  
Author(s):  
XIULI ZhANG ◽  
JIANHUI QU ◽  
GANG SUN ◽  
JING YANG ◽  
YUNSHENG YANG
Keyword(s):  
Gastric Cancer ◽  
Simultaneous Detection ◽  
Gene Mutations ◽  
Chinese Patients

scholarly journals Influence of target gene mutations on survival, stage and histology in sporadic microsatellite unstable colon cancers

2006 ◽  
Vol 118 (10) ◽  
pp. 2509-2513 ◽  
Author(s):  
Barbara Jung ◽  
E. Julieta Smith ◽  
Ryan T. Doctolero ◽  
Pascal Gervaz ◽  
Julio C. Alonso ◽  
...  
Keyword(s):  
Target Gene ◽  
Gene Mutations ◽  
Colon Cancers

scholarly journals Molecular characteristics of synchronous multiple gastric cancer

Theranostics ◽  
2020 ◽  
Vol 10 (12) ◽  
pp. 5489-5500
Author(s):  
Anqiang Wang ◽  
Zhongwu Li ◽  
Meng Wang ◽  
Shuqin Jia ◽  
Jiahu Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Molecular Characteristics ◽  
Multiple Gastric Cancer

scholarly journals DNA Methylation and Genetic Aberrations in Gastric Cancer

Digestion ◽  
2020 ◽  
pp. 1-8
Author(s):  
Genki Usui ◽  
Keisuke Matsusaka ◽  
Yasunobu Mano ◽  
Masayuki Urabe ◽  
Sayaka Funata ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Dna Methylation ◽  
Tyrosine Kinases ◽  
Cpg Islands ◽  
Gene Mutations ◽  
Gastric Carcinogenesis ◽  
The Cancer Genome Atlas ◽  
Dna Hypermethylation ◽  
Genomic Amplification ◽  
Genetic Aberrations

<b><i>Background:</i></b> Gastric cancer (GC) is one of the leading causes of cancer-related deaths worldwide. GC is a pathologically and molecularly heterogeneous disease. DNA hypermethylation in promoter CpG islands causes silencing of tumor-suppressor genes and thus contributes to gastric carcinogenesis. In addition, various molecular aberrations, including aberrant chromatin structures, gene mutations, structural variants, and somatic copy number alterations, are involved in gastric carcinogenesis. <b><i>Summary:</i></b> Comprehensive DNA methylation analyses revealed multiple DNA methylation patterns in GCs and classified GC into distinct molecular subgroups: extremely high-methylation epigenotype uniquely observed in GC associated with Epstein-Barr virus (EBV), high-methylation epigenotype associated with microsatellite instability (MSI), and low-methylation epigenotype. In The Cancer Genome Atlas classification, EBV and MSI are extracted as independent subgroups of GC, whereas the remaining GCs are categorized into genomically stable (GS) and chromosomal instability (CIN) subgroups. EBV-positive GC, exhibiting the most extreme DNA hypermethylation in the whole human malignancies, frequently shows <i>CDKN2A</i> silencing, <i>PIK3CA</i> mutations, <i>PD-L1/2</i> overexpression, and lack of <i>TP53</i> mutations. MSI, exhibiting high DNA methylation, often has <i>MLH1</i> silencing and abundant gene mutations. GS is generally a diffuse-type GC and frequently shows <i>CDH1/RHOA</i> mutations or <i>CLDN18–ARHGAP</i> fusion. CIN is generally an intestinal-type GC and frequently has <i>TP53</i> mutations and genomic amplification of receptor tyrosine kinases. <b><i>Key Messages:</i></b> The frequency and targets of genetic aberrations vary depending on the epigenotype. Aberrations in the genome and epigenome are expected to synergistically interact and contribute to gastric carcinogenesis and comprehensive analyses of those in GCs may help elucidate the mechanism of carcinogenesis.

Oncogenic mutations in MAPK cascade as novel molecular biomarkers for treatment of gastric cancer patients with EGFR inhibitors.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 39-39
Author(s):  
G. Corso ◽  
D. Marrelli ◽  
V. Pascale ◽  
L. Garosi ◽  
S. Velho ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Association Studies ◽  
Gene Mutations ◽  
Mapk Cascade ◽  
Egfr Inhibitors ◽  
Mitogen Activated Protein Kinase ◽  
Gastrointestinal Malignancies ◽  
Gastric Carcinomas ◽  
Egfr Expression ◽  
Oncogenic Mutations

39 Background: Mitogen-activated protein kinase (MAPK) cascade and phosphatidylinositol 3-kinase (PI3K) survival pathways are frequently activated in the progression of gastrointestinal malignancies. In this study, we aimed to determine the frequency of gene mutations in members of these pathways-EGFR, KRAS, BRAF, PIK3CA and MLK3 in a series of 63 gastric carcinomas with high levels of microsatellite instability. Methods: Gene mutation analysis was performed by PCR amplification followed by direct sequencing. In selected tumor cases, EGFR expression was evaluated by immunohistochemistry. Association studies between molecular data and clinicopathologic characteristics were performed. Results: Mutations in EGFR (3'-UTR polyA repeat), KRAS, PIK3CA and MLK3 genes occurred in 30 (47.6%), 11 (17.5%), 9 (14.3%) and 2 (3.2%) of the MSI gastric cancer (GC) cases, respectively. No BRAF or EGFR hotspot mutations were identified. Overall, mutations in at least one of these genes were found in 55.6% (35/63) of gastric carcinomas. From those mutant cases 40.0% (14/35) of them had concomitant gene mutations, always involving EGFR polyA deletions. Interestingly, we observed significant associations between oncogenic mutations and female gender (p=0.046) old age of diagnosis (p=0.001) and intestinal subtype (p=0.043). Conclusions: Our results show that MSI gastric carcinoma frequently shows activation of EGFR-MAPK and PI3K pathways. Within all alterations found, deletions of the A13 repeats of EGFR were common, suggesting this molecular event as an important biomarker for stratification of GC patients for treatment with EGFR inhibitors. No significant financial relationships to disclose.

Searching for CDH1 gene mutations in early-onset diffuse gastric cancer in Chinese patients.

2014 ◽  
Vol 32 (3_suppl) ◽  
pp. 23-23
Author(s):  
Xu Yanjun ◽  
Cao Wenming ◽  
Xu Qi ◽  
Guo Jianmin ◽  
Wang Xinbao ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Gene Mutations ◽  
Germline Mutations ◽  
Chinese Patients ◽  
Diffuse Gastric Cancer ◽  
Cdh1 Gene ◽  
Node Metastasis ◽  
Cdh1 Mutation

23 Background: CDH1 germline mutations are found to be associated with the development of hereditary diffuse gastric cancer (HDGC) and the early-onset diffuse gastric cancer (EODGC). But the impact of CDH1 gene mutations and large deletions on HDGC and EODGC has not been fully determined in Asians. Although the incidence of gastric cancer is relatively high in China, the detection rate of CDH1 germline mutations in Chinese patients with EODGC is rare compared to that in European patients. Methods: We investigated the mutation status of the CDH1 gene in 57 Chinese EODGC patients younger than 40 years old who met the clinical criteria for HDGC. Polymerase chain reaction-direct sequencing was performed, and multiplex ligation-dependent probe amplification (MLPA) was used to evaluate the patients with negative sequencing results. Associations between mutation, clinicopathologic, and overall survival data were analyzed by SPSS 19. Results: The germline mutations of CDH1gene were identified in 51 (89.5%) of the 57 EODGC patients. The nonsense mutation in exon 13 (c.2200T>C, p.Ala692*) occurred in fourty-six EODGC patients. The missense mutations were detected in twenty patients (Eighteen in exon 5: c.778G>C, p.Glu218Asp; Two in exon 12: c.2012C>G, p.Leu630Val). No deletion or duplication in any patient. Most of the patients carrying the CDH1 mutation in exon 13 had lymph node metastasis when compared with patients lacking CDH1 mutation (87.2% vs 60.0%) ( P < 0.05 ). EODGC patients, lacking germline CDH1 alterations, showed a longer median overall survival (mOS) than patients carrying CDH1 mutation in exon 13 ( P < 0.05 ). Moreover, the presence of CDH1 mutation in exon 13 was associated with the incidence of neural invasion ( P < 0.05 ). Conclusions: This study reveals novel CDH1 mutations in Chinese EODGC patients which had been poorly investigated. The presence of CDH1 mutation in EODGC patients may result in lymph node metastasis and poor prognosis. More research is needed to determine additional genetic targets that trigger EODGC.

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