CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients

Debouki-Joudi, Saoussen; Trifa, Fatma; Khabir, Abdelmajid; Sellami‐Boudawara, Tahya; Frikha, M.; Daoud, J.; Mokdad-Gargouri, Raja

doi:10.3233/cbm-160005

Cited by 14 publications

(8 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…MGMT is involved in the DNA repair process, protecting against the activity of alkylating agents, and caused the alkylated guanidine to revert to its natural state by transferring an alkyl group to specific cysteine residues of MGMT ( 57 ). The APC (adenomatous polyposis coli) promoter is also known to be methylated in aggressive forms of breast cancer and other cancers ( 58 ) and serves as an inhibitor of Wnt signaling ( 59 ).…”

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Tumor Suppressors byHelicobacter pyloriEnhances EBV-Induced Proliferation of Gastric Epithelial Cells

Pandey

Jha

Shukla

et al. 2018

mBio

View full text Add to dashboard Cite

Helicobacter pylori and Epstein-Barr virus (EBV) are two well-known contributors to cancer and can establish lifelong persistent infection in the host. This leads to chronic inflammation, which also contributes to development of cancer. Association with H. pylori increases the risk of gastric carcinoma, and coexistence with EBV enhances proliferation of infected cells. Further, H. pylori-EBV coinfection causes chronic inflammation in pediatric patients. We have established an H. pylori-EBV coinfection model system using human gastric epithelial cells. We showed that H. pylori infection can increase the oncogenic phenotype of EBV-infected cells and that the cytotoxin-associated gene (CagA) protein encoded by H. pylori stimulated EBV-mediated cell proliferation in this coinfection model system. This led to increased expression of DNA methyl transferases (DNMTs), which reprogrammed cellular transcriptional profiles, including those of tumor suppressor genes (TSGs), through hypermethylation. These findings provide new insights into a molecular mechanism whereby cooperativity between two oncogenic agents leads to enhanced oncogenic activity of gastric cancer cells.

show abstract

Section: Discussionmentioning

confidence: 99%

Epigenetic Regulation of Tumor Suppressors byHelicobacter pyloriEnhances EBV-Induced Proliferation of Gastric Epithelial Cells

Pandey

Jha

Shukla

et al. 2018

mBio

View full text Add to dashboard Cite

show abstract

“…[32] It was found that APC gene promoter methylation was 52.1% in sporadic BC cases, and there was a significant relationship of APC hypermethylation with tumor stage and 3-year survival (p<0.05). [33] In the present study, the APC gene methylation was 43.3%. No association was found between RASSF1A/APC methylation status and histopathological type, grade and ER/PR status.…”

Section: Rassf1a/apc Methylationsupporting

confidence: 48%

Correlation of HER2/TOP2A Gene Aberrations with RASSF1A/APC Gene Methylation Status in High-Risk Breast Cancer

NURSAL

2020

TJ Oncol

View full text Add to dashboard Cite

Breast cancer (BC) is a heterogeneous malignancy and differs widely among different patients. The aim of this study was to investigate the relationship between the HER2/TOP2A gene aberrations and promoter methylation in RASSF1A/APC genes in patients with high-risk BC. METHODS Formalin-fixed paraffin embedded (FFPE) tissue samples from primary breast tumors (n=60) were assessed. HER2/TOP2A aberrations was evaluated using FISH method. DNA was extracted from FFPE tumor tissues, and Methylation-sensitive high resolution melting (MS-HRM) analysis were performed for RASSF1A/APC genes methylation status. RESULTS HER2 amplification and TOP2A aberration were observed in 15/60 (25%) and 18/60 (30%) cases, respectively. According to the statistical analysis, HER2 amplification was associated with higher tumor grade (p=0.001), PR status (p=0.025), and TOP2A aberrations (p=0.004). RASSF1A and APC methylation were 58/60 (96.6%) and 26/60 (43.3%), respectively. There was a significant correlation between APC methylation and TOP2A aberration. APC gene methylation was significantly more frequent in tumors with TOP2A aberration (p=0.026). CONCLUSION Our results suggested that APC gene promoter hypermethylation was associated with TOP2A gene aberrations in patients with high-risk BC. This may be significant for targeted individual therapy. Additionally, it was confirmed that there was significant association of TOP2A gene aberrations with the HER2 gene amplification seen in BC.

show abstract

“…[285,286]) were observed in about 70% of inflammatory breast cancers [287], as well as in some 90% of lung cancers [288,289] (and prostate cancers [290][291][292]). This rate was equaled in both sporadic and familial breast cancer [293], again questioning the role of mutations as being causal to the majority of cancers.…”

Section: Chronic Inflammationmentioning

confidence: 98%

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Brücher

Jamall

2019

4open

View full text Add to dashboard Cite

A pathogenic (biological or chemical) stimulus is the earliest information received by a cell that can result in the disruption of homeostasis with consequent development of disease. Chronic inflammation involves many cell types with numerous cytokines and signaling pathways, the release of different components by the cells, and the crosstalk provoked by such stimuli involving subclinical chronic inflammation and is mechanistically manifold. Exosomes secrete chemicals that trigger the epithelium to produce exosome-like nanoparticles promoting chronic inflammation. Small molecules, together with various cytokines, selectively target signaling pathways inducing crosstalk that suppress apoptosis. 16S rRNA gene sequencing has become routine to provide information on the composition and abundance of bacteria found in human tissues and in reservoirs. The deregulation of autophagy with chronic stimulation of inflammation is an early phenomenon in carcinogenesis. The disruption of cell–cell integrity enables transcellular CagA migration and triggers deregulation of autophagy with the net result being chronic inflammation. The complex and insidious nature of chronic inflammation can be seen both inside and outside the cell and even with intracellular nuclear fragments such as chromatin, which itself can elicit a chronic inflammatory response within the cytoplasm and affect autophagy. The ultimate result of unresolved chronic inflammation is fibrosis, a step before tissue remodeling results in the formation of a precancerous niche (PCN). Various pathogenic stimuli associated with different neoplasms result in persistent inflammation. This ongoing disruption of homeostasis in the micromilieu of cells, tissues, and organs is an essential preamble to carcinogenesis and occurs early in that process.

show abstract

CpG methylation of APC promoter 1A in sporadic and familial breast cancer patients

Cited by 14 publications

References 34 publications

Epigenetic Regulation of Tumor Suppressors byHelicobacter pyloriEnhances EBV-Induced Proliferation of Gastric Epithelial Cells

Epigenetic Regulation of Tumor Suppressors byHelicobacter pyloriEnhances EBV-Induced Proliferation of Gastric Epithelial Cells

Correlation of HER2/TOP2A Gene Aberrations with RASSF1A/APC Gene Methylation Status in High-Risk Breast Cancer

Chronic inflammation evoked by pathogenic stimulus during carcinogenesis

Contact Info

Product

Resources

About