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Published on: February 16, 2024
[Epigenetics in the pathogenesis and early detection of gastric cancer]
Abstract:
Gastric cancer is the first cause of death for cancer in Chile. The recently identified genetic alterations in these tumors have not yielded new biomarkers for the disease. Epigenetics or the study of reversible genomic changes that do not affect protein codifying DNA sequences but cause phenotypic disturbances, is identifying new cancer biomarkers. Specifically, the loss of expression caused by the covalent link of a methyl group to carbon 5 of cytosine (DNA hypermethylation) is extensively evaluated. Performing an epigenetic evaluation of 24 genes, we have identified eight genes associated to the aggressive signet ring cell type gastric cancer, the association between APC hypermethylation and worse prognosis and BRCA1 hypermethylation association with early onset of gastric cancer. The most interesting findings are the hypermethylation of Reprimo gene in plasma as a population biomarker and the tissue over expression of p73 gene (as a consequence of hypomethylation) as a high risk indicator of progression to gastric cancer. All these findings are indicating an important role of epigenetics in the pathogenesis and early detection of gastric cancer.
Insights
Epigenetic alterations, including DNA hypermethylation, are key to understanding gastric cancer. This study identified new epigenetic biomarkers for early detection and prognosis of this deadly disease.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Context:
- Gastric cancer is a leading cause of cancer death in Chile.
- Genetic alterations have not yielded effective gastric cancer biomarkers.
- Epigenetics offers novel biomarkers for cancer detection and prognosis.
Purpose:
- To investigate epigenetic alterations as potential biomarkers for gastric cancer.
- To identify specific epigenetic changes associated with gastric cancer subtypes and outcomes.
Summary:
- An epigenetic evaluation of 24 genes identified eight associated with signet ring cell gastric cancer.
- APC hypermethylation correlates with poorer prognosis, while BRCA1 hypermethylation is linked to early-onset disease.
- Reprimo gene hypermethylation in plasma shows potential as a population biomarker.
- Tissue overexpression of p73 (due to hypomethylation) indicates a high risk of gastric cancer progression.
Impact:
- These findings highlight epigenetics' crucial role in gastric cancer pathogenesis.
- Identified biomarkers could improve early detection and risk stratification for gastric cancer.
- Reprimo and p73 epigenetic markers offer new avenues for diagnostic and prognostic tools in gastric cancer.
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