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EPCAM mutation update: Variants associated with congenital tufting enteropathy and Lynch syndrome
Author(s) -
Pathak Sagar J.,
Mueller James L.,
Okamoto Kevin,
Das Barun,
Hertecant Jozef,
Greenhalgh Lynn,
Cole Trevor,
Pinsk Vered,
Yerushalmi Baruch,
Gurkan Odul E.,
Yourshaw Michael,
Hernandez Erick,
Oesterreicher Sandy,
Naik Sandhia,
Sanderson Ian R.,
Axelsson Irene,
Agardh Daniel,
Boland C. Richard,
Martin Martin G.,
Putnam Christopher D.,
Sivagnanam Mamata
Publication year - 2019
Publication title -
human mutation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 162
eISSN - 1098-1004
pISSN - 1059-7794
DOI - 10.1002/humu.23688
Subject(s) - epithelial cell adhesion molecule , lynch syndrome , frameshift mutation , missense mutation , biology , mutation , genetics , msh2 , splice site mutation , cancer research , dna mismatch repair , cancer , gene , colorectal cancer , exon , alternative splicing
The epithelial cell adhesion molecule gene ( EPCAM , previously known as TACSTD1 or TROP1 ) encodes a membrane‐bound protein that is localized to the basolateral membrane of epithelial cells and is overexpressed in some tumors. Biallelic mutations in EPCAM cause congenital tufting enteropathy (CTE), which is a rare chronic diarrheal disorder presenting in infancy. Monoallelic deletions of the 3′ end of EPCAM that silence the downstream gene, MSH2 , cause a form of Lynch syndrome, which is a cancer predisposition syndrome associated with loss of DNA mismatch repair. Here, we report 13 novel EPCAM mutations from 17 CTE patients from two separate centers, review EPCAM mutations associated with CTE and Lynch syndrome, and structurally model pathogenic missense mutations. Statistical analyses indicate that the c.499dupC (previously reported as c.498insC) frameshift mutation was associated with more severe treatment regimens and greater mortality in CTE, whereas the c.556‐14A>G and c.491+1G>A splice site mutations were not correlated with treatments or outcomes significantly different than random simulation. These findings suggest that genotype–phenotype correlations may be useful in contributing to management decisions of CTE patients. Depending on the type and nature of EPCAM mutation, one of two unrelated diseases may occur, CTE or Lynch syndrome.