Linked Life Data

17986858

Source:http://linkedlifedata.com/resource/pubmed/id/17986858

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2008-4-28
pubmed:abstractText
The hypermethylation of tumor-suppressor gene promoter regions has been shown to result in the epigenetic inactivation of many genes. ASC/TMS1 is a pro-apoptotic gene that has been shown to be methylated in many different human neoplasms. The methylation status of ASC/TMS1 was analyzed in a series of colorectal cancer (CRC) cell lines, adenomas and primary colorectal cancers and normal colorectal tissue samples using methylation-specific PCR (MSP). The gene expression of ASC/TMS1 in the CRC cell lines was analyzed using reverse-transcriptase PCR (RT-PCR). Methylation analysis showed complete methylation of ASC/TMS1 in 5 of 7 (71%) CRC cell lines. RT-PCR showed absence of mRNA expression in these same cell lines, and expression was restored after treatment with the demethylating drug 5-aza-2'-deoxyazacytidine. The two unmethylated cell lines showed ASC/TMS1 mRNA expression both before and after treatment with 5-aza-2'-deoxyazacytidine. Methylation was seen in 20 of 115 (17%) of primary colorectal cancer specimens, but no methylation was seen in 30 colorectal adenomas and 11 normal colorectal tissue samples. Methylation status of ASC/TMS1 was correlated with a series of clinicopathological variables using multivariate analysis. Methylation of ASC/TMS1 was more common in right-sided tumors (p = 0.02), concordant with hMLH1 methylation (p = 0.03) and is a late stage event, occurring in 0 of 18 tubular adenomas, 0 of 12 villous adenomas, 2 of 44 (5%) Stage 1 cancers, 8 of 31 (26%) Stage 2 cancers, 8 of 21 (38%) Stage 3 cancers and 2 of 19 (11%) Stage 4 cancers. The ASC/TMS1 gene is frequently silenced in CRC due to promoter hypermethylation. Methylation of ASC/TMS1 appears to be a late-stage event in colorectal carcinogenesis associated with invasive carcinomas but not with normal colorectal tissue or colorectal adenomas. Methylation of ASC/TMS1 may have implications for cancer prognosis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1555-8576
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
6
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1710-6
pubmed:meshHeading
pubmed:year
2007
pubmed:articleTitle
Methylation-induced silencing of ASC/TMS1, a pro-apoptotic gene, is a late-stage event in colorectal cancer.
pubmed:affiliation
Department of Surgery, Johns Hopkins University, Baltimore, Maryland, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't