ISSN : 2146-3123
E-ISSN : 2146-3131

Targeted Next Generation Sequencing of MLH1, MSH2, and MSH6 Genes in Patients with Endometrial Carcinoma <50 Years of Age
Taha Reşid Özdemir1, Murat Alan2, Muzaffer Sancı2, Altuğ Koç1
1Genetic Diagnostic Center, Health Sciences University, İzmir Tepecik Training and Research Hospital, İzmir, Turkey
2Department of Gynecology and Gynecologic Oncology, Health Sciences University, İzmir Tepecik Training and Research Hospital, İzmir, Turkey
DOI : 10.4274/balkanmedj.2018.0922

Background: Lynch syndrome (LS), which is an inherited cancer disorder, has an increased lifetime risk for various cancers. Endometrial cancer (EC) is the most common extra-colonic cancer in LS. Guidelines recommend that patients with EC diagnosed under 50 years of age should be evaluated for LS. Molecular analysis of mismatch repair (MMR) genes and EPCAM gene is required for a definitive diagnosis of LS.
Aims: The purpose of this study was to report the mutation analysis of MMR genes using targeted next generation sequencing (NGS) in patients having EC diagnosed <50 years of age as the first study from Turkey, to our knowledge.
Study Design: Retrospective cross-sectional study.
Methods: Seventy-nine patients with EC diagnosed <50 years of age underwent genetic counseling. They were selected among 1094 consecutive EC patients between 2006 and 2017. Molecular analysis of MLH1, MSH2, and MSH6 genes was performed in 79 patients by using NGS. And also, deletion/duplication analysis of MMR genes and EPCAM gene was performed in 79 patients by using multiplex ligation-dependent probe amplification (MLPA) method.
Results: Germline testing of MMR genes was performed in 79 EC patients. LS 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, 10 variants as variants of uncertain significance (VUS).
Conclusion: This study emphasized that Lynch syndrome should be investigated in patients having EC diagnosed under 50 years of age because of increased lifetime risk for various cancers and this study determined the mutation frequency in MMR genes as the first time in Turkish patients with EC diagnosed <50 years of age by revealing both known and novel variants using NGS.

Keywords : Lynch syndrome, endometrial cancer, targeted next generation sequencing, mismatch repair genes, novel mutation

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