Background The identification of pathogenic mutations in genes that increase the risk of ovarian cancer has an impact on the clinical management of patients, including decisions about surveillance, chemoprevention, and risk-reducing surgical interventions. Mutations in hereditary cancer susceptibility genes account for up to 20% of ovarian cancers in the US.
Objectives To analyze the mutations detected using a multigene panel in patients with a personal history of ovarian cancer and evaluate the emerging use of panel testing.
Methods We identified 3,088 patients with ovarian cancer whose samples had been submitted to a large commercial laboratory for genetic testing with a 25-gene hereditary-risk panel. The frequency and spectrum of mutations were analyzed according to clinical factors (ancestry, age at testing, testing criteria).
Results Deleterious or suspected deleterious mutations were identified in 419 patients (13.6%), 7 of whom had mutations in 2 different genes. Testing patients using the 25-gene panel increased the number of positive test results in ovarian cancer patients by 53.8% over BRCA1/2 testing alone, showing the benefit of using a panel approach in this population. In all, 27.2% of patients with positive test results had mutations that would not have been identified by single-syndrome genetic testing for hereditary breast and ovarian cancer or Lynch syndrome.
Limitations Clinical histories collected by test request form; retrospective study.
Conclusions Our results demonstrate the benefits of multigene panels for patients with personal history of ovarian cancer, particularly for the identification of moderate-penetrance mutations that would not otherwise be identified by single-syndrome testing.
Funding Myriad Genetic Laboratories
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