|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
5
|
|
pubmed:dateCreated |
2010-2-5
|
|
pubmed:abstractText |
Hereditary diffuse gastric cancer (HDGC) is an autosomal dominant cancer susceptibility syndrome characterized by early-onset diffuse gastric cancer (DGC) and lobular breast cancer. E-cadherin (CDH1) heterozygous germline mutations and deletions are found in 40% of families. Independent of CDH1 alterations, most HDGC tumours display mislocalized or absent E-cadherin immunoexpression, therefore undetected defects at the CDH1 locus may still be involved. We aimed at determining whether CDH1 mutation-negative probands display germline CDH1 allele-specific expression (ASE) imbalance, using a single-nucleotide primer extension-based procedure and tried to uncover the underlying molecular defect. CDH1 ASE analysis was performed using three intragenic SNPs in RNA extracted from the blood of 21 cancer-free individuals and 22 HDGC probands (5 CDH1 mutation carriers and 17 CDH1 negative). Germline promoter methylation, deletions and haplotype-related susceptibility at the CDH1 locus were analysed. Both CDH1 alleles from cancer-free individuals displayed equivalent expression levels, whereas monoallelic CDH1 expression or high allelic expression imbalance (AI) was present in 80% of CDH1 mutant and 70.6% (n = 12) of CDH1-negative HDGC probands. Germline deletions and promoter hypermethylation were found in 25% of probands displaying high CDH1 AI. No particular haplotype was found to be associated with CDH1 high AI. Germline CDH1 AI is highly frequent among CDH1 mutation-negative probands but was not seen in cancer-free individuals. This implicates the CDH1 locus in the majority of mutation-negative HDGC families.
|
|
pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-10469842,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-10644736,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-10842743,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-10973239,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-11253064,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-11254454,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-11729114,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-11743581,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-12444556,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-14574645,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-16061854,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-16285940,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-16501831,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-16951683,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-17267408,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-17660459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18006746,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18059179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18204050,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18427545,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18462018,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18482459,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18703712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18772194,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-18788075,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19098912,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19168852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19269290,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19346325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19406134,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19455606,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19565498,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-19671196,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-2574768,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-3960115,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-7493024,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-8247073,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-8988179,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-9322509,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-9537325,
http://linkedlifedata.com/resource/pubmed/commentcorrection/19965908-9751616
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
1460-2083
|
|
pubmed:author |
pubmed-author:Bordeira-CarriçoRenataR,
pubmed-author:CarvalhoJoanaJ,
pubmed-author:GusmãoLeonorL,
pubmed-author:HuntsmanDavidD,
pubmed-author:InácioPatríciaP,
pubmed-author:OliveiraCarlaC,
pubmed-author:OliveiraPatríciaP,
pubmed-author:PinheiroHugoH,
pubmed-author:RochaJorgeJ,
pubmed-author:SeixasSusanaS,
pubmed-author:SenzJanineJ,
pubmed-author:SerucaRaquelR
|
|
pubmed:issnType |
Electronic
|
|
pubmed:day |
1
|
|
pubmed:volume |
19
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
943-52
|
|
pubmed:dateRevised |
2011-7-25
|
|
pubmed:meshHeading |
|
|
pubmed:year |
2010
|
|
pubmed:articleTitle |
Allele-specific CDH1 downregulation and hereditary diffuse gastric cancer.
|
|
pubmed:affiliation |
Institute of Molecular Pathology and Immunology, University of Porto (IPATIMUP), Porto 4200-465, Portugal.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
