2013
DOI: 10.1186/1897-4287-11-9
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Germline deletions in the EPCAM gene as a cause of Lynch syndrome – literature review

Abstract: Lynch syndrome (clinically referred to as HNPCC – Hereditary Non-Polyposis Colorectal Cancer) is a frequent, autosomal, dominantly-inherited cancer predisposition syndrome caused by various germline alterations that affect DNA mismatch repair genes, mainly MLH1 and MSH2. Patients inheriting this predisposition are susceptible to colorectal, endometrial and other extracolonic tumors. It has recently been shown that germline deletions of the last few exons of the EPCAM gene are involved in the etiology of Lynch … Show more

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Cited by 122 publications
(99 citation statements)
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“…Those findings are similar to results from other studies 6 . Recent studies have proposed that the proteolytic cleavage of epcam-icd triggers a signalling cascade leading to the activation of the Wnt/ beta-catenin pathway 3 . Cleaved epcam-icd binds to adaptor protein fhl-2 and beta-catenin in the cytoplasm, and the resulting complex translocates to the nucleus, where it upregulates c-Myc and cyclins A and E gene transcription, leading to tumorigenesis and progression 25 -a process that is supported by our finding that loss of membranous epcam-icd immunohistochemical staining is associated with lesser 5-year survival, high preoperative cea, and poor tumour differentiation.…”
Section: Discussionmentioning
confidence: 99%
See 1 more Smart Citation
“…Those findings are similar to results from other studies 6 . Recent studies have proposed that the proteolytic cleavage of epcam-icd triggers a signalling cascade leading to the activation of the Wnt/ beta-catenin pathway 3 . Cleaved epcam-icd binds to adaptor protein fhl-2 and beta-catenin in the cytoplasm, and the resulting complex translocates to the nucleus, where it upregulates c-Myc and cyclins A and E gene transcription, leading to tumorigenesis and progression 25 -a process that is supported by our finding that loss of membranous epcam-icd immunohistochemical staining is associated with lesser 5-year survival, high preoperative cea, and poor tumour differentiation.…”
Section: Discussionmentioning
confidence: 99%
“…It is thought to be involved in calcium-independent cell adhesion, signalling, migration, proliferation, and differentiation 1 extracellular domain (ex) with both epidermal growth factor and thyroglobulin repeat-like domains, a transmembrane domain, and a relatively short intracellular domain (icd) 2 . Proteolytic cleavage of epcam leads to the creation of an extracellular domain (epcam-ex) and an intracellular domain (epcam-icd) that consists of a short 26-amino-acid fragment that has been shown to trigger activation of the Wnt/beta-catenin pathway and aggressive tumour behavior 2,3 . In addition, formation of an epcam-icd-beta-catenin complex with other proteins has been shown to lead to transcription and upregulation of several genes, including c-Myc and CCND1, which might promote tumour growth 4 .…”
Section: Introductionmentioning
confidence: 99%
“…As described above, the MMR system plays a critical role in preserving genetic fidelity (Kunkel and Erie, 2005;Tutlewska et al, 2013). After initial detection of replication errors by the heterodimers MSH2/MSH6 (MutS␣) and MSH2/MSH3 (MutS␤), subsequent recruitment of the MLH1/PMS2 complex degrades the mutated segment and initiates resynthesis of the DNA (Li, 2008).…”
Section: The Mismatch Repair Gene Systemmentioning
confidence: 99%
“…It should be noted that occasional cases of MSH2/ MSH6 loss are due to deletions of the 3 0 end of EPCAM, a gene just upstream of MSH2. 10 However, this is well known to geneticists, and the germline evaluation of MSH2 typically includes a test for EPCAM deletions.…”
Section: Msi Vs Ihcmentioning
confidence: 99%