Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
5
pubmed:dateCreated
2000-4-11
pubmed:abstractText
We recently showed loss of pRb in a proportion of pituitary tumors that was not associated with loss of heterozygosity of an RB1 intragenic marker. To further define the mechanism responsible for loss of retinoblastoma protein (pRb) expression, we have investigated the methylation status of the CpG island contained within the promoter region of the RB1 gene, together with sequence analysis of the essential promoter region and exons coding for the protein-binding pocket domain. Methylation of the CpG island within the RB1 promoter region was detected in 6 of 10 tumors that failed to express pRb. In contrast, 18 of 20 tumors and all six histologically normal postmortem pituitaries that expressed pRb were unmethylated. No inactivating mutations were found within the RB1 promoter region in the four unmethylated tumors that failed to express pRB. However, one or more exons comprising the coding region for the protein-binding pocket domain were shown to be homozygously deleted in three of four tumors available for analysis. This study describes an additional tumor type, in addition to retinoblastoma, in which methylation of the RB1 promoter is associated with loss of pRb expression. Furthermore, we show that in addition to methylation of the RB1 promoter region, deletion within the protein-binding pocket domain is associated with a loss of detectable pRb expression. The reactivation of tumor suppressor genes, silenced through methylation, represents a promising therapeutic target in sporadic pituitary adenomas.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0008-5472
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
60
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1211-6
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
2000
pubmed:articleTitle
Loss of pRb expression in pituitary adenomas is associated with methylation of the RB1 CpG island.
pubmed:affiliation
Centre for Cell and Molecular Medicine, School of Postgraduate Medicine, Keele University, North Staffordshire Hospital, Stoke-on-Trent, United Kingdom.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't