Universal Germline Genetic Testing in a Precision Oncology and Rare Cancer Clinic: Implementation and Outcomes

Area of Science:

• Oncology
• Genetics
• Cancer Predisposition Syndromes

Background:

• National Comprehensive Cancer Network (NCCN) guidelines for germline testing are complex and may miss eligible patients.
• Germline genetic testing is crucial for identifying hereditary cancer susceptibility.
• Evaluating universal germline testing in a precision medicine setting is essential.

Purpose of the Study:

• To assess the prevalence of pathogenic/likely pathogenic (P/LP) germline variants through universal germline testing.
• To determine the proportion of patients with cancer susceptibility missed by NCCN guidelines.
• To compare findings between patients with rare and common cancers.

Main Methods:

• Universal germline genetic testing was performed on 120 consenting cancer patients (55 common, 65 rare) at a Precision Oncology and Rare Cancer clinic.
• Patients met with a clinic-embedded genetic counselor prior to testing.
• Data collected included cancer type, germline test results, and NCCN guideline eligibility.

Main Results:

• A 15% positive rate for P/LP germline variants was observed (13% common, 17% rare cancers).
• 50% of patients with positive germline variants did not meet NCCN testing criteria.
• High/moderate penetrance variants were found in 83% (common) and 42% (rare) of positive cases.

Conclusions:

• Universal germline testing identifies clinically actionable variants missed by NCCN guidelines, revealing guideline limitations.
• Inclusive testing strategies are necessary for comprehensive cancer predisposition identification.
• Clinic-embedded genetic counselors play a vital role in facilitating testing and counseling.