Rescreening for genetic mutations using multi-gene panel testing in patients who previously underwent non-informative genetic screening ★

• The utility of panel testing in patients with prior single gene testing is unclear.
• Rescreening of 127 patients identified nine patients with pathogenic mutations.
• Rescreening identified 53 patients with VUS not identified on prior screening.
• The clinical implications of VUS, a common finding, remain unknown.

ObjectiveThe availability of next-generation sequencing and identification of multiple cancer-related genes has caused a shift away from single gene testing towards multi-gene panel testing for hereditary cancer syndromes. However, the utility of panels in individuals who previously underwent non-informative genetic screening has yet to be evaluated. We aim to evaluate the use of rescreening and results of multi-gene panels in this rescreened population.MethodsWe reviewed the medical records for patients who had previously undergone genetic testing and then underwent multi-gene panel testing at a single institution between 9/2013 and 11/2014.ResultsOne hundred and twenty-seven patients with prior genetic testing underwent multi-gene panels. One hundred and four patients (82%) had a history of cancer and 118 (93%) had at least one family member with cancer. On primary testing, no pathogenic mutations were detected and 10 patients (8%) were found to have variants of uncertain significance (VUS). On repeat multi-gene panel testing, nine patients (7%) were found to have a pathogenic mutation and 53 patients (42%) were VUS not identified on prior testing.ConclusionsSeven percent of patients with non-informative primary testing were found to have a pathogenic mutation with multi-gene panels, suggesting that there is a potential benefit to be gained from rescreening. However, 42% of patients were found to have new VUS with panels, a result that can cause patients anxiety without clear clinical implications.