Double Trouble: EPCAM Exon 9 Deletion in Lynch Syndrome Leading to Dual Primary Tumors

Lynch syndrome (LS) is one of the most widely recognized cancer susceptibility syndromes and is caused by germline mutations of the mismatch repair (MMR) genes MLH1, MSH2, PMS2, and MSH6. One of the less commonly known mechanisms is the deletion of the 3’ end of the Epithelial Cell Adhesion Molecule (EPCAM) gene, which is closely situated to the MSH2 gene promoter. Such deletion causes hypermethylation of the MSH2 gene promoter and leads to its inactivation. This case reports a young adult diagnosed with two metachronous primary tumors due to a germline EPCAM exon 9 deletion and subsequent MSH2 gene inactivation, shedding light on one of the most underrecognised pathways of microsatellite instability.