Integrated Analysis Of Genetic And Epigenetic Alterations In Cancer

Abstract

A proposed genetic model describing the transition from normal colonic epithelium to malignant cancer involves mutation of a number of key oncogenes and tumor suppressor genes. However, only subsets of colorectal cancers contain such mutations. Moreover, the heterogeneous pattern of tumor mutations suggests there are multiple alternative pathways leading to colonic tumorigenesis. These alternative pathways involve epigenetic alterations such as the methylation of multiple CpG islands, termed the CpG island methylator phenotype, and cancers with CpG island methylator phenotype show distinct genetic and clinicopathological features. The causes of these epigenetic alterations are still not fully understood, but exogenous pathogens such as Helicobacter pylori and Epstein–Barr virus, and the chromosomal translocations seen in leukemia, have all been shown to induce epigenetic alterations of genes.

KEYWORDS::

• CpG island methylator phenotype
• colorectal cancer
• DNA methylation
• epigenetics
• histone
• tumor suppressor gene

Acknowledgements

The authors thank William F Goldman for editing the manuscript.

Financial & competing interests disclosure

This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology (Kohzoh Imai and Minoru Toyota), Grants-in-Aid for Scientific Research (S) from Japan Society for Promotion of Science (Kohzoh Imai), a Grant-in-Aid for the Third-term Comprehensive 10-year Strategy for Cancer Control, and Grant-in-Aid for Cancer Research from the Ministry of Health, Labor, and Welfare, Japan (Minoru Toyota). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

This study was supported in part by Grants-in-Aid for Scientific Research on Priority Areas from the Ministry of Education, Culture, Sports, Science, and Technology (Kohzoh Imai and Minoru Toyota), Grants-in-Aid for Scientific Research (S) from Japan Society for Promotion of Science (Kohzoh Imai), a Grant-in-Aid for the Third-term Comprehensive 10-year Strategy for Cancer Control, and Grant-in-Aid for Cancer Research from the Ministry of Health, Labor, and Welfare, Japan (Minoru Toyota). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.