Germline Variants of the MMR/EPCAM Genes in Russian Patients with Lynch Syndrome

Lynch syndrome is the most common hereditary cancer syndrome caused by pathogenic variants in the MMR/EPCAM genes. The aim of this work was to study the germline variants of these genes in the largest sample of patients with Lynch syndrome in Russia. The study included all data on pathogenic and likely pathogenic variants in the MMR/EPCAM genes taken from the Center’s local Registry of hereditary forms of colorectal cancer. We analyzed all available data from 141 probands with Lynch syndrome: 78 men and 63 women aged 21 to 80 years who were treated in our Center from 2012 to 2023. The number of pathogenic and likely pathogenic variants found in the key genes were MLH1 – 69, MSH2 – 57, MSH6 – 10, EPCAM – 3, PMS2 – 1, PMS1 – 1. Among 141 germline variants, 17 (12.1%) were found for the first time: MLH1 – 8, MSH2 – 8, MSH6 – 1. Thirteen (9.2%) of the identified variants were related to large deletions/duplications. The most frequent pathogenic variants in the MLH1 gene were: c.1852_1854del (9 probands), c.350C>T (4) and c.1459C>T (3), and in the MSH2 gene: c.942+3A>T (9) and c.1288A>T (3). The results obtained have made it possible to establish the frequency and range of different types of germline variants in the MMR/EPCAM genes, which made it possible to optimize the algorithm for selection and diagnosing Russian patients with Lynch syndrome.