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Risks and Implications of Multiple Actionable Pathogenic Germline Variants Discovered by Panel-Based Cancer
Catherine Neumann1, Demitrios Dedousis1,2, Michael J Hall1
1Department of Clinical Genetics, Fox Chase Cancer Center, Philadelphia, PA.
The growing use of multigene panels (MGPs) identifies more patients with multiple pathogenic germline variants (PGVs). A significant portion of these patients benefit from management changes due to multiple PGVs.
Area of Science:
- Genetics
- Oncology
- Clinical Diagnostics
Background:
- Multigene panels (MGPs) are increasingly used for genetic testing.
- This leads to a rise in identifying patients with multiple pathogenic germline variants (PGVs).
- Understanding the implications of multiple PGVs is crucial for patient management.
Purpose of the Study:
- To characterize the landscape of patients identified with multiple PGVs.
- To identify clinical settings where multiple PGVs impact patient management decisions.
Main Methods:
- Retrospective cohort analysis of patients evaluated with MGPs.
- Inclusion of patients with multiple PGVs from a single institution's registry.
- Data collected from January 1, 2014, to January 1, 2024.
Main Results:
- 0.8% (64/7,961) of patients carried multiple PGVs.
- 34% had at least two PGVs in high- or moderate-risk genes.
- 52% had PGVs that could lead to management changes, including 10 patients with both BRCA1/2 and mismatch repair (MMR) gene PGVs.
Conclusions:
- While uncommon, multiple PGVs are identified in a small percentage of patients undergoing genetic testing.
- A significant fraction of these patients can benefit from altered medical management strategies.
- Identifying multiple PGVs is clinically relevant for cancer predisposition management.
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