Research Article| Volume 165, ISSUE 3, P546-551, June 2022

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Utility of germline multi-gene panel testing in patients with endometrial cancer


      • Germline multigene panel testing (MGPT) can identify cancer susceptibility alleles that may otherwise go undetected.
      • MGPT found mutations in non-Lynch cancer susceptibility genes in 6% of EC patients with positive family histories of cancer.
      • Such mutations have implications for clinical care, including enhanced screening and risk reduction practices.
      • MGPT revealed additional Lynch syndrome cases not identified on routine tumor-based screening.



      Patients with germline mutations in mismatch repair genes (MLH1, MSH2, MSH6, PMS2) associated with Lynch syndrome (LS) have an increased lifetime risk of endometrial cancer (EC). Multi-gene panel testing (MGPT) is a recent hereditary cancer risk tool enabling next-generation sequencing of numerous genes in parallel. We determined the prevalence of actionable cancer predisposition gene mutations identified through MGPT in an EC patient cohort.


      A single center retrospective cohort study was conducted of patients with EC who had a clinical indication for genetic testing and who underwent MGPT as part of standard of care treatment between 2012 and 2021. Pathogenic mutations were identified and actionable mutations were defined as those with clinical management implications. Additionally, the number of individuals identified with LS was compared between MGPT and tumor-based screening.


      The study included a total of 224 patients. Thirty-three patients [14.7%, 95% confidence interval (CI) = 10.4–20.1] had actionable mutations. Twenty-one patients (9.4%, 95% CI = 5.9–14.0) had mutations in LS genes (4 MLH1, 5 MSH2, 7 MSH6, 4 PMS2, 1 Epcam-MSH2). MGPT revealed two patients with LS (9.5% of LS cases) not identified through routine tumor-based screening. Thirteen patients (5.8%, 95% CI = 3.1–9.7) had at least one actionable mutation in a non-Lynch syndrome gene (6 CHEK2, 2 BRCA2, 2 ATM, 2 APC, 1 RAD51C, 1 BRCA1).


      Germline MGPT is both feasible and informative as it identifies LS cases not found on tumor testing as well as additional actionable mutations in patients with EC.


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