Associated disorders

The EPCAM gene is associated with autosomal dominant Lynch syndrome (also called hereditary nonpolyposis colorectal cancer syndrome, or HNPCC) (MedGen UID: 40399) and autosomal recessive congenital tufting enteropathy (MedGen UID: 413031). Deletions at the 3’ end of EPCAM are known to cause Lynch syndrome through inactivation of MSH2, whereas pathogenic sequence changes are known to cause congenital tufting enteropathy and have not been reported to cause Lynch syndrome.

EPCAM (epithelial cell adhesion molecule) encodes a carcinoma-associated antigen that functions as a cell-adhesion molecule and is involved in cell signaling and migration, as well as embryonic stem cell proliferation and differentiation. This protein also has oncogenic potential due to its capacity to upregulate c-myc, e-fabp, and cyclins A&E.

  1. Kohlmann, W, Gruber, SB. Lynch Syndrome. 2004 Feb 05. In: Pagon, RA, et al, editors. GeneReviews (Internet). University of Washington, Seattle; Available from: http://www.ncbi.nlm.nih.gov/books/NBK1211/ PMID: 20301390
  2. Salomon, J, et al. A founder effect at the EPCAM locus in Congenital Tufting Enteropathy in the Arabic Gulf. Eur J Med Genet. 2011; 54(3):319-22. doi: 10.1016/j.ejmg.2011.01.009. PMID: 21315192
  3. Ligtenberg, MJ, et al. EPCAM deletion carriers constitute a unique subgroup of Lynch syndrome patients. Fam. Cancer. 2013; 12(2):169-74. doi: 10.1007/s10689-012-9591-x. PMID: 23264089
  4. Niessen, RC, et al. Germline hypermethylation of MLH1 and EPCAM deletions are a frequent cause of Lynch syndrome. Genes Chromosomes Cancer. 2009; 48(8):737-44. doi: 10.1002/gcc.20678. PMID: 19455606
  5. Bakry, D, et al. Genetic and clinical determinants of constitutional mismatch repair deficiency syndrome: report from the constitutional mismatch repair deficiency consortium. Eur. J. Cancer. 2014; 50(5):987-96. doi: 10.1016/j.ejca.2013.12.005. PMID: 24440087
  6. Sivagnanam, M, et al. Identification of EpCAM as the gene for congenital tufting enteropathy. Gastroenterology. 2008; 135(2):429-37. doi: 10.1053/j.gastro.2008.05.036. PMID: 18572020
  7. Rahner, N, et al. Clinical utility gene card for: Lynch syndrome (MLH1, MSH2, MSH6, PMS2, EPCAM) - update 2012. Eur. J. Hum. Genet. 2013; 21(1):None. doi: 10.1038/ejhg.2012.164. PMID: 22892529
  8. Tutlewska, K, et al. Germline deletions in the EPCAM gene as a cause of Lynch syndrome - literature review. Hered Cancer Clin Pract. 2013; 11(1):9. doi: 10.1186/1897-4287-11-9. PMID: 23938213

Assay and technical information

Invitae is a College of American Pathologists (CAP)-accredited and Clinical Laboratory Improvement Amendments (CLIA)-certified clinical diagnostic laboratory performing full-gene sequencing and deletion/duplication analysis using next-generation sequencing technology (NGS).

Our sequence analysis covers clinically important regions of each gene, including coding exons, +/- 10 base pairs of adjacent intronic sequence, and select noncoding variants. Our assay provides a Q30 quality-adjusted mean coverage depth of 350x (50x minimum, or supplemented with additional analysis). Variants classified as pathogenic or likely pathogenic are confirmed with orthogonal methods, except individual variants that have high quality scores and previously validated in at least ten unrelated samples.

Our analysis detects most intragenic deletions and duplications at single exon resolution. However, in rare situations, single-exon copy number events may not be analyzed due to inherent sequence properties or isolated reduction in data quality. If you are requesting the detection of a specific single-exon copy number variation, please contact Client Services before placing your order.

Gene Transcript reference Sequencing analysis Deletion/Duplication analysis
EPCAM* NM_002354.2

*EPCAM: Analysis is limited to deletion/duplication analysis