Linked Life Data

11598162

Source:http://linkedlifedata.com/resource/pubmed/id/11598162

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2001-10-12
pubmed:abstractText
Loss of the cell adhesion molecule E-cadherin has been observed in a variety of human carcinomas, and germline E-cadherin mutations have been found in several familial cases of diffuse gastric cancer. We sought to determine the prevalence and nature of E-cadherin alterations in "sporadic" gastric carcinomas. We performed comprehensive sequencing of the coding region, loss of heterozygosity (LOH) analysis, and immunohistochemical protein expression determination on 40 sporadic gastric adenocarcinomas. In total, 7 of 25 diffuse-type cancers harbored genetic alterations in the E-cadherin gene. Novel mutations predicted to significantly compromise protein function were found within 4 of these cancers, 2 of which harbored alterations resulting in biallelic inactivation of the gene product. Three diffuse cancers failed to amplify Exon 8 of E-cadherin, suggesting the presence of a homozygous abnormality. Notably, one germline E-cadherin mutation was also identified within these "sporadic" diffuse cancers. Significant gene mutations were not found in the 14 intestinal-type or histologically mixed cancer. Immunohistochemistry revealed aberrant or negative protein expression in seven diffuse-type tumors, four of which correlated with the genetic alterations. Both diffuse and intestinal-type tumors exhibited low rates of LOH, suggesting that allelic loss at the locus is not a common mechanism for E-cadherin inactivation during gastric tumorigenesis. Our observations suggest that inactivation of the E-cadherin gene occurs only in a subset of diffuse-type gastric cancers, as the majority of cases did not contain genetic alterations or identifiable protein abnormalities. Germline E-cadherin alterations, although rare, may underlie some diffuse gastric cancer cases that have important biologic and practical implications
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0893-3952
pubmed:author
pubmed:issnType
Print
pubmed:volume
14
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
942-9
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Inactivation of the E-cadherin gene in sporadic diffuse-type gastric cancer.
pubmed:affiliation
Department of Medicine, University of Virginia Health System, Charlottesville, Virginia 22908, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't