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Genome-Wide Analysis of DNA Methylation in Gastrointestinal Cancer
Published on: September 18, 2020
DNA Methylation Profiling of MYC, SMAD2/3 and DNMT3A in Colorectal Cancer
Seyedeh Elham Norollahi1, Maryam Gholamniya Foumani2, Maryam Khoshbakht Pishkhan3
1Cancer Research Center and Department of Immunology, Semnan University of Medical Sciences, Semnan, Iran.
Abstract:
Epigenetic modifications, particularly DNA methylation, is commonplace and a remarkable factor in carcinogenesis transformation. Conspicuously, previous findings have presented a cluster of irregular promoter methylation alterations related with silencing of tumor suppressor genes, little is accepted regarding their sequential DNA methylation (hypo and hyper) modifications during the cancer progression. In this way, fluctuations of DNA methylation of many genes, especially MYC, SMAD2/3, and DNMT3A, have an impressive central key role in many different cancers, including colorectal cancer (CRC). CRC is distinguished by DNA methylation, which is related to tumorigenesis and also genomic instability. Importantly, molecular heterogeneity between multiple adenomas in different patients with CRC may show diverse developmental phenotypes for these kinds of tumors. Conclusively, studying factors that are involved in CRC carcinogenesis, especially the alterations in epigenetic elements, such as DNA methylation besides RNA remodeling, and histone modification, acetylation and phosphorylation, can be influential to find new therapeutic and diagnostic biomarkers in this type of malignancy. In this account, we discuss and address the potential significant methylated modifications of these genes and their importance during the development of CRC carcinogenesis.
Insights
DNA methylation changes are key in cancer development, especially colorectal cancer (CRC). Understanding these epigenetic shifts in genes like MYC and DNMT3A can reveal new diagnostic and therapeutic biomarkers for CRC.
Area of Science:
- Oncology
- Epigenetics
- Molecular Biology
Background:
- Epigenetic modifications, particularly DNA methylation, are crucial in cancer development.
- Aberrant promoter methylation is linked to tumor suppressor gene silencing.
- The sequential DNA methylation changes (hypo- and hypermethylation) during cancer progression are not well understood.
Purpose of the Study:
- To investigate the role of sequential DNA methylation alterations in colorectal cancer (CRC) carcinogenesis.
- To highlight the importance of specific gene methylation changes (MYC, SMAD2/3, DNMT3A) in CRC development.
- To explore epigenetic factors as potential biomarkers for CRC diagnosis and therapy.
Main Methods:
- Review and discussion of existing literature on DNA methylation in cancer.
- Focus on sequential methylation patterns (hypo- and hypermethylation).
- Analysis of key genes implicated in CRC, including MYC, SMAD2/3, and DNMT3A.
Main Results:
- DNA methylation alterations are a hallmark of CRC, contributing to tumorigenesis and genomic instability.
- Specific genes like MYC, SMAD2/3, and DNMT3A exhibit significant methylation fluctuations during CRC progression.
- Molecular heterogeneity in CRC suggests diverse developmental pathways influenced by epigenetic changes.
Conclusions:
- Studying sequential DNA methylation, alongside other epigenetic modifications like histone modification and RNA remodeling, is vital for understanding CRC carcinogenesis.
- Identifying specific methylated modifications in key genes can lead to novel therapeutic strategies and diagnostic biomarkers for colorectal cancer.
- Epigenetic alterations play a significant role in the molecular heterogeneity and progression of colorectal cancer.

