Highlights
- •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.
Abstract
Objectives
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.
Methods
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.
Results
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).
Conclusions
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.
Keywords
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Article info
Publication history
Published online: April 25, 2022
Accepted:
April 6,
2022
Received in revised form:
April 1,
2022
Received:
January 21,
2022
Identification
Copyright
© 2022 Published by Elsevier Inc.
