Epigenetic Study of PCDH10 Gene in Colorectal Cancer
Date Issued
2008
Date
2008
Author(s)
Chang, Chia-Yun
Abstract
Colorectal cancer (CRC) is one of the most common malignancies and is the third leading cause of cancer death in Taiwan. Most sporadic CRCs are thought to develop from benign adenomas to carcinoma. The two major pathways in colorectal carcinogenesis, LOH (loss of heterozygosity) and MSI (microsatellite instability), accumulate different genetic abnormalities. Tumorigenesis is not only linked to genetic alteration as a contribution but also to epigenetic regulation as a major player in cancer development. DNA methylation remains the best-studied epigenetic mechanism. Methylation at the C-5 position of cytosine residues present in CpG dinucleotides by DNA methyltransferases (DNMTs). This methylation inhibits gene expression by directly blocking the binding of transcription factors (TFs) to the target gene promoter sequence. Tumor suppressor genes (TSGs) silencing by DNA methylation has been found in many cases of cancer. In our preliminary study of LOH frequency on chromosome 4 in cases of CRC, three LOH loci were frequently defined around 4q25-4q28.3. A cell adhesion molecule, protocadherin 10 (PCDH10), is located in one of these regions. In a recent study, PCDH10 was identified as a candidate TSG due to frequent silencing in nasopharyngeal, esophageal, lymphoma and multiple other carcinomas by DNA methylation. However, there is little known about PCDH10 methylation in CRC. Therefore, the purpose of this study was to deremine whether PCDH10 expression is regulated by DNA methylation. We analyzed the frequency of PCDH10 methylation in CRC cell lines and patient tissue samples. Our studies revealed that PCDH10 was highly methylated in both CRC cell lines and CRC tissues. Methylation of PCDH10 between tumor tissues of CRC patients and adjacent normal mucosa was significant, but was not necessarily correlated to age, sex, tumor location, tumor differentiation, or Dukes'' stage. On the other hand, the colon cancer cell, SW620, once treated with an epigenetic demethylation drug, 5-aza-2''-deoxycytidine (5-Aza-CdR), can restore PCDH10 RNA expression. Thus, PCDH10 expression is regulated by epigenetic modification and is frequently methylated in CRC.
Subjects
Colorectal cancer
Epigenetic modification
DNA methylation
SDGs
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