Frequency of deletions of EPCAM (TACSTD1) in MSH2-associated Lynch syndrome cases

J Mol Diagn. 2011 Jan;13(1):93-9. doi: 10.1016/j.jmoldx.2010.11.011. Epub 2010 Dec 23.


Lynch syndrome is an autosomal dominant cancer predisposition syndrome characterized by loss of function of DNA mismatch repair enzyme MLH1, MSH2, MSH6, or PMS2. Mutations in MLH1 and MSH2 account for ∼80% of the inherited cases. However, in up to 20% of cases suspected of having a germline mutation in MSH2 due to loss of MSH2 expression, a germline mutation is not identified. Recent studies have shown that some Lynch syndrome cases are due to 3' EPCAM/TACSTD1 deletions that subsequently lead to MSH2 promoter hypermethylation. In this study, we examined the frequency of this novel mechanism for MSH2 inactivation in cases recruited through the Colon Cancer Family Registry and from the Mayo Clinic Molecular Diagnostics Laboratory. From the combined cohort, 58 cases were selected in which immunohistochemical staining suggested a mutation in MSH2 or MSH6, but no mutations were identified on follow-up testing. Of these 58 cases, 11 demonstrated a deletion of EPCAM/TACSTD1. Of cases with a deletion, the methylation status of the MSH2 promoter was confirmed in tumor tissue using methylation-sensitive PCR primers. One case showed MSH2 promoter hypermethylation in the absence of a detectable EPCAM/TACSTD1 deletion. These results indicate that approximately 20% to 25% of cases suspected of having a mutation in MSH2 but in which a germline mutation is not detected, can be accounted for by germline deletions in EPCAM/TACSTD1. These data also suggest the presence of other alterations leading to MSH2 promoter hypermethylation.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Adult
  • Aged
  • Antigens, Neoplasm / genetics*
  • Cell Adhesion Molecules / genetics*
  • Colonic Neoplasms / genetics
  • Colorectal Neoplasms, Hereditary Nonpolyposis / genetics*
  • DNA Methylation
  • DNA Mismatch Repair
  • Epithelial Cell Adhesion Molecule
  • Female
  • Humans
  • Ligase Chain Reaction
  • Male
  • Microsatellite Instability
  • Middle Aged
  • MutS Homolog 2 Protein / genetics*
  • Promoter Regions, Genetic
  • Sequence Deletion*


  • Antigens, Neoplasm
  • Cell Adhesion Molecules
  • EPCAM protein, human
  • Epithelial Cell Adhesion Molecule
  • MSH2 protein, human
  • MutS Homolog 2 Protein