Open AccessLynch Syndrome-Associated Extracolonic Tumors Are Rare in Two Extended Families With the Same EPCAM Deletion
Author(s) -
Henry T. Lynch,
Douglas L. RiegertJohnson,
Carrie L. Snyder,
Jane F. Lynch,
Jill Hagenkord,
C. Richard Boland,
Jennifer Rhees,
Stephen N. Thibodeau,
Lisa A. Boardman,
Janine Marie Davies,
Roland P. Kuiper,
Nicoline Hoogerbrugge,
Marjolijn J. L. Ligtenberg
Publication year - 2011
Publication title -
the american journal of gastroenterology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.907
H-Index - 252
eISSN - 1572-0241
pISSN - 0002-9270
DOI - 10.1038/ajg.2011.203
Subject(s) - epithelial cell adhesion molecule , lynch syndrome , mlh1 , msh6 , msh2 , microsatellite instability , pms2 , cancer research , endometrial cancer , colorectal cancer , medicine , cancer , mutation , genetics , biology , dna mismatch repair , gene , microsatellite , allele
The Lynch syndrome (LS) is an inherited cancer syndrome showing a preponderance of colorectal cancer (CRC) in context with endometrial cancer and several other extracolonic cancers, which is due to pathogenic mutations in the mismatch repair (MMR) genes, MLH1, MSH2, MSH6, and PMS2. Some families were found to show a LS phenotype without an identified MMR mutation, although there was microsatellite instability and absence of MSH2 expression by immunohistochemistry. Studies of a subset of these families found a deletion at the 3' end of the epithelial cell adhesion molecule (EPCAM) gene, causing transcription read-through resulting in silencing of MSH2 through hypermethylation of its promoter. The tumor spectrum of such families appears to differ from classical LS.