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Epigenetic changes in colorectal cancer.
Yutaka Kondo1, Jean-Pierre J Issa
1Department of Leukemia, University of Texas at M.D. Anderson Cancer Center, Houston, Texas 77030, USA.
Cancer Metastasis Reviews
|March 6, 2004
Summary
Epigenetic silencing, driven by DNA methylation and histone changes, inactivates tumor-suppressor genes in colorectal cancers (CRCs). These early epigenetic alterations are crucial in cancer development and progression.
Area of Science:
- Oncology
- Molecular Biology
- Genetics
Background:
- Epigenetic silencing is a key mechanism in cancer, complementing genetic mutations.
- DNA methylation and histone modifications are primary mediators of epigenetic inheritance in cancer cells.
- Aberrant epigenetic changes are linked to neoplastic transformation in colorectal cancers (CRCs).
Purpose of the Study:
- To explore the role of epigenetic alterations in colorectal cancer development.
- To understand the mechanisms of tumor-suppressor gene inactivation via epigenetic pathways.
- To highlight the significance of DNA methylation and histone modifications in CRCs.
Main Methods:
- Analysis of DNA methylation patterns in gene promoters.
- Investigation of histone modification alterations.
- Correlation of epigenetic changes with neoplastic transformation and cancer progression in CRCs.
Main Results:
- Aberrant DNA methylation occurs early in colon mucosa, potentially contributing to sporadic CRCs.
- The CpG Island Methylator Phenotype (CIMP) is a hypermethylator phenotype defining about half of sporadic CRCs.
- DNA methylation and histone modifications form a silencing loop, inactivating tumor-suppressor genes in CRCs.
Conclusions:
- Epigenetic alterations are a significant driving force in colorectal cancer initiation and progression.
- Understanding these epigenetic changes offers new avenues for CRC research, risk assessment, and treatment.
- Epigenetic silencing represents a critical 'third pathway' in tumor-suppressor gene inactivation.