Targeted Next-Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma under 50 Years of Age

BACKGROUND: Lynch syndrome is an inherited cancer disorder that causes an increased lifetime risk of various types of cancers. Endometrial cancer is the most common extracolonic cancer in Lynch syndrome. Guidelines recommend that patients with endometrial cancer younger than 50 years of age should be evaluated for Lynch syndrome. Molecular analysis of the mismatch repair genes and EPCAM gene is required for a definitive diagnosis of Lynch syndrome. AIMS: To report the mutation analysis of mismatch repair genes using targeted next-generation sequencing in endometrial cancer diagnosed patients <50 years of age. STUDY DESIGN: Retrospective cross-sectional study. METHODS: Seventy-nine endometrial cancer diagnosed patients <50 years of age underwent genetic counseling. They were selected among 1094 consecutive endometrial cancer patients between 2006 and 2017. Molecular analysis of MLH1, MSH2, and MSH6 genes was performed in 79 patients by using next-generation sequencing. Deletion/duplication analysis of mismatch repair genes and EPCAM gene was also performed in 79 patients by using the multiplex ligation-dependent probe amplification method. RESULTS: Germline testing of mismatch repair genes was performed in 79 endometrial cancer patients. Lynch syndrome was confirmed in 4 patients (5%; 4/79). A total of 14 variants (6 in MSH2, 5 in MLH1, 3 in MSH6 genes) were found in 14 patients. Four variants were assessed as pathogenic/likely pathogenic, and 10 variants were assessed as variants of uncertain significance. CONCLUSION: Lynch syndrome should be investigated in patients diagnosed with endometrial cancer that are less than 50 years of age due to the increased lifetime risk of developing cancer.