Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2002-1-24
pubmed:abstractText
High-frequency microsatellite instability (MSI-H) due to defective DNA mismatch repair occurs in the majority of hereditary nonpolyposis colorectal cancers (HNPCCs) and in a subset of sporadic malignant tumors. Clinicopathologic and genotypic features of MSI-H colorectal tumors in HNPCC patients and those in sporadic cases are very similar but not identical. Correlation between the MSI phenotype and aberrant DNA methylation has been highlighted recently. A strong association between MSI and CpG island methylation has been well characterized in sporadic colorectal cancers with MSI-H but not in those of hereditary origin. To address the issue, we analyzed hereditary and sporadic colorectal cancers for aberrant DNA methylation of target genes using methylation-specific polymerase chain reaction. DNA methylation of the MLH1, CDKN2A, MGMT, THBS1, RARB, APC, and p14ARF genes was found in 0%, 23%, 10%, 3%, 73%, 53%, and 33% of 30 MSI-H cancers in HNPCC patients and in 80%, 55%, 23%, 23%, 58%, 35%, and 50% of 40 sporadic colorectal cancers with MSI-H, respectively. Cases showing methylation at three or more loci of six genes other than MLH1 were defined as CpG island methylator phenotype-positive (CIMP +), and 23% of HNPCC tumors and 53% of sporadic cancers with MSI-H were CIMP+ (P = 0.018). Differences in the extent of CpG island methylation, coupled with the differential involvement of several genes by methylation, in HNPCC tumors and sporadic MSI-H colorectal cancers may be associated with diverging developmental pathways in hereditary and sporadic cancers despite similar MSI-H phenotypes.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1045-2257
pubmed:author
pubmed:copyrightInfo
Copyright 2002 Wiley-Liss, Inc.
pubmed:issnType
Print
pubmed:volume
33
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
322-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed:year
2002
pubmed:articleTitle
Differential involvement of the hypermethylator phenotype in hereditary and sporadic colorectal cancers with high-frequency microsatellite instability.
pubmed:affiliation
First Department of Internal Medicine, Sapporo Medical University, Sapporo, Japan. h-yama@sapmed.ac.jp
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't