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Yonsei Med J. 2009 Jun;50(3):309-321.
Published online 2009 June 23.  doi: 10.3349/ymj.2009.50.3.309.
© Copyright: Yonsei University College of Medicine 2009
Promoter Methylation in the Genesis of Gastrointestinal Cancer
Clement Richard Boland,1 Sung Kwan Shin,1,2 and Ajay Goel1
1Division of Gastroenterology, Department of Internal Medicine, Sammons Cancer Center, Baylor Research Institute, Baylor University Medical Center, Dallas, Texas, USA.
2Division of Gastroenterology, Department of Internal Medicine, Institute of Gastroenterology, Yonsei University College of Medicine, Seoul, Korea.

Corresponding author: Dr. Clement Richard Boland, GI Cancer Research Laboratory (H-250), Baylor University Medical Center, 3500 Gaston Avenue, Dallas, TX 75246, USA. Tel: 214-820-2692, Fax: 214-818-9292, Email: RickBo@BaylorHealth.edu
Received March 26, 2009.

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted noncommercial use, distribution, and reproduction in any medium, provided the original work is properly cited.


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.

Keywords: Colorectal cancer, promoter methylation, CIMP, Lynch syndrome, HNPCC, microsatellite instability, chromosomal instability, hepatocellular carcinoma.
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