Editorial
Copyright ©2007 Baishideng Publishing Group Co., Limited. All rights reserved.
World J Gastroenterol. Mar 28, 2007; 13(12): 1767-1769
Published online Mar 28, 2007. doi: 10.3748/wjg.v13.i12.1767
Microsatellite instability and MLH1 promoter hypermethylation in colorectal cancer
Yaron Niv
Yaron Niv, Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Tel Aviv University, Israel
Author contributions: All authors contributed equally to the work.
Correspondence to: Professor Yaron Niv, Chief of Department of Gastroenterology, Rabin Medical Center, Beilinson Hospital, Petah Tikva 49100, Israel. nivyaron@013.net.il
Telephone: +972-3-9377237 Fax: +972-3-9210313
Received: March 7, 2007
Revised: March 9, 2006
Accepted: March 12, 2007
Published online: March 28, 2007
Abstract

Colorectal cancer (CRC) is caused by a series of genetic or epigenetic changes, and in the last decade there has been an increased awareness that there are multiple forms of colorectal cancer that develop through different pathways. Microsatellite instability is involved in the genesis of about 15% of sporadic colorectal cancers and most of hereditary nonpolyposis cancers. Tumors with a high frequency of microsatellite instability tend to be diploid, to possess a mucinous histology, and to have a surrounding lymphoid reaction. They are more prevalent in the proximal colon and have a fast pass from polyp to cancer. Nevertheless, they are associated with longer survival than stage-matched tumors with microsatellite stability. Resistance of colorectal cancers with a high frequency of microsatellite instability to 5-fluorouracil-based chemotherapy is well established. Silencing the MLH1 gene expression by its promoter methylation stops the formation of MLH1 protein, and prevents the normal activation of the DNA repair gene. This is an important cause for genomic instability and cell proliferation to the point of colorectal cancer formation. Better knowledge of this process will have a huge impact on colorectal cancer management, prevention, treatment and prognosis.

Keywords: MLH1; Methylation; Colorectal cancer; Micro-satellite instability; CpG island methylator phenotype; Chromosomal instability