Promoter Methylation in the Genesis of Gastrointestinal Cancer.
10.3349/ymj.2009.50.3.309
- Author:
Clement Richard BOLAND
1
;
Sung Kwan SHIN
;
Ajay GOEL
Author Information
1. Division of Gastroenterology, Department of Internal Medicine, Sammons Cancer Center, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA. RickBo@BaylorHealth.edu
- Publication Type:Review ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
- Keywords:
Colorectal cancer;
promoter methylation;
CIMP;
Lynch syndrome;
HNPCC;
microsatellite instability;
chromosomal instability;
hepatocellular carcinoma
- MeSH:
Colorectal Neoplasms/genetics;
DNA Methylation/*genetics;
Gastrointestinal Neoplasms/*etiology/*genetics;
Humans;
Microsatellite Instability;
Promoter Regions, Genetic/*genetics
- From:Yonsei Medical Journal
2009;50(3):309-321
- CountryRepublic of Korea
- Language:English
-
Abstract:
Colorectal cancers (CRC)-and probably all cancers-are caused by alterations in genes. This includes activation of oncogenes and inactivation of tumor suppressor genes (TSGs). There are many ways to achieve these alterations. Oncogenes are frequently activated by point mutation, gene amplification, or changes in the promoter (typically caused by chromosomal rearrangements). TSGs are typically inactivated by mutation, deletion, or promoter methylation, which silences gene expression. About 15% of CRC is associated with loss of the DNA mismatch repair system, and the resulting CRCs have a unique phenotype that is called microsatellite instability, or MSI. This paper reviews the types of genetic alterations that can be found in CRCs and hepatocellular carcinoma (HCC), and focuses upon the epigenetic alterations that result in promoter methylation and the CpG island methylator phenotype (CIMP). The challenge facing CRC research and clinical care at this time is to deal with the heterogeneity and complexity of these genetic and epigenetic alterations, and to use this information to direct rational prevention and treatment strategies.
