RNA Analysis Identifies Pathogenic Duplications in MSH2 in Patients With Lynch Syndrome

Clinical DNA genetic testing (DGT) for Lynch syndrome (LS) has increased in recent years, helping clarify cancer risks with one important caveat: variants of unknown significance (VUS). VUS pose challenges to physicians because there are no well-defined guidelines for the clinical management of LS patients with VUS.1 Among the LS genes, MSH2 has the highest number of germline structural variants (SV), such as exonic inversions, deletions, and duplications.2 The vast majority of deletions and inversions are pathogenic.