Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2006-5-10
pubmed:abstractText
Esophageal squamous cell carcinoma (ESCC) is a common cancer with a very poor prognosis. New methods are needed to screen high-risk populations and identify curable tumors and precursor lesions early. Molecular markers may be useful in such screening efforts. This study was designed to determine the prevalence of p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in patients with ESCC to evaluate the variation of gene methylation across a spectrum of preneoplastic lesions, and assess the feasibility of using gene methylation in a primary screening test utilizing frozen esophageal cells collected by balloon cytology samplers. Samples were obtained from high-risk subjects from north central China. These samples included 11 foci of histologically normal mucosa, 8 foci of low-grade squamous dysplasia, 7 foci of high-grade squamous dysplasia, and 13 foci of ESCC from 6 fully embedded resection specimens; endoscopic biopsies from 6 individuals with no histological evidence of disease; and frozen esophageal balloon samples from 12 asymptomatic subjects. Promoter CpG site-specific hypermethylation status was determined for each gene using real-time methylation-specific PCR (qMS-PCR) based on Taqman chemistry. Of the 6 ESCC patients, 5 showed methylation of at least one gene. For most genes, methylation occurred with increasing frequency during neoplastic progression, with the largest increase found between low- and high-grade dysplasia. There was considerable variation in methylation patterns among different foci of the same histological grade, even within individual patients, but 16/20 (80%) of high-grade dysplastic and cancer foci had >or= 2 methylated genes, while 17/19 (89%) of normal and low-grade dysplastic foci had <2 methylated genes. These genes were rarely methylated in histologically normal mucosa from patients with or without ESCC. Gene methylation was common and easily detectable in the frozen esophageal cells collected by balloon cytology samplers. Our data suggest that methylation of p16, MGMT, RARbeta2, CLDN3, CRBP, and MT1G is common in the esophageal mucosa of patients with ESCC in this high-risk population, and tends to increase in prevalence in foci with increasing histological severity of disease. Methylation data from panels of genes may be able to identify patients with high-grade lesions. Balloon cytology may be able to screen the length of the esophagus effectively for a subset of cells with abnormal methylation, and may be useful in a primary screening test for ESCC and its precursor lesions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/DNA Modification Methylases, http://linkedlifedata.com/resource/pubmed/chemical/DNA Repair Enzymes, http://linkedlifedata.com/resource/pubmed/chemical/MGMT protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Metallothionein, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Retinoic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Retinol-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/Retinol-Binding Proteins, Cellular, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Protein p14ARF, http://linkedlifedata.com/resource/pubmed/chemical/Tumor Suppressor Proteins, http://linkedlifedata.com/resource/pubmed/chemical/claudin 3, http://linkedlifedata.com/resource/pubmed/chemical/retinoic acid receptor beta
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
1021-335X
pubmed:author
pubmed:issnType
Print
pubmed:volume
15
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1591-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16685400-Adult, pubmed-meshheading:16685400-Aged, pubmed-meshheading:16685400-Carcinoma, Squamous Cell, pubmed-meshheading:16685400-DNA Methylation, pubmed-meshheading:16685400-DNA Modification Methylases, pubmed-meshheading:16685400-DNA Repair Enzymes, pubmed-meshheading:16685400-Esophageal Neoplasms, pubmed-meshheading:16685400-Female, pubmed-meshheading:16685400-Genes, p16, pubmed-meshheading:16685400-Humans, pubmed-meshheading:16685400-Male, pubmed-meshheading:16685400-Membrane Proteins, pubmed-meshheading:16685400-Metallothionein, pubmed-meshheading:16685400-Middle Aged, pubmed-meshheading:16685400-Precancerous Conditions, pubmed-meshheading:16685400-Receptors, Retinoic Acid, pubmed-meshheading:16685400-Retinol-Binding Proteins, pubmed-meshheading:16685400-Retinol-Binding Proteins, Cellular, pubmed-meshheading:16685400-Tumor Suppressor Protein p14ARF, pubmed-meshheading:16685400-Tumor Suppressor Proteins
pubmed:year
2006
pubmed:articleTitle
p16, MGMT, RARbeta2, CLDN3, CRBP and MT1G gene methylation in esophageal squamous cell carcinoma and its precursor lesions.
pubmed:affiliation
National Cancer Institute, 6120 Executive Blvd, EPS/320, MSC 7232, Rockville, MD 20892, USA. mr166i@nih.gov
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural, Research Support, N.I.H., Intramural