Title: EPCAM germline and somatic rearrangements in lynch syndrome: identification of a novel 3 ' EPCAM deletion
Authors: Spaepen, Marijke ×
Neven, Esther
Sagaert, Xavier
De Hertogh, Gert
Beert, Eline
Wimmer, Katharina
Matthijs, Gert
Legius E, Eric
Brems, Hilde #
Issue Date: Sep-2013
Publisher: Wiley-Liss, Inc.
Series Title: Genes, Chromosomes & Cancer vol:52 issue:9 pages:845-854
Article number: 10.1002/gcc.22080
Abstract: 3'EPCAM (Epithelial Cell Adhesion Molecule) genomic rearrangements can be a cause of mismatch repair deficiency in rare Lynch syndrome families. 3'EPCAM deletions include the polyadenylation signal and might result in promoter hypermethylation of the centromeric MSH2 gene in cis. A somatic rearrangement in trans affecting MSH2 is responsible for the final mismatch repair deficiency in the corresponding tumors but the mechanisms are not well documented. In this report two germline 3'EPCAM deletions are described together with the corresponding somatic mutations in the patient's colorectal tumors. Mutation and breakpoint analysis resulted in the identification of one novel (c.556-531_*872del) and one known EPCAM deletion (c.859-689_*14697del). Both deletions resulted from Alu mediated homologous recombination causing aberrant EPCAM-MSH2 fusion transcripts. The colorectal tumors of the deletion carriers were MSI-high. Strong hypermethylation of the MSH2 promoter was measured. Analysis of somatic genomic rearrangements showed a 4 Mb deletion including the EPCAM, MSH2 and MSH6 genes in one tumor and copy neutral loss of heterozygosity in the EPCAM-MSH2 region in the other tumor. This indicates that hemi- and homozygous hypermethylation of the MSH2 promoter and hence complete silencing of MSH2 expression was responsible for the mismatch repair deficiency in both colorectal tumors. © 2013 Wiley Periodicals, Inc.
ISSN: 1045-2257
Publication status: published
KU Leuven publication type: IT
Appears in Collections:Department of Human Genetics - miscellaneous
Translational Cell & Tissue Research
Biology, Campus Kulak Kortrijk
Department of Biology - miscellaneous
Laboratory for Neurofibromatosis Research
× corresponding author
# (joint) last author

Files in This Item:

There are no files associated with this item.

Request a copy


All items in Lirias are protected by copyright, with all rights reserved.

© Web of science