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Discrepancies between tumor genomic profiling and germline genetic testing.
K Pauley1, C Koptiuch1, S Greenberg1
1Family Cancer Assessment Clinic, Huntsman Cancer Institute, Salt Lake City, USA.
ESMO Open
|July 3, 2022
Summary
Tumor genomic profiling can miss important germline pathogenic variants (PVs). Discrepancies between somatic and germline testing impact patient management and treatment, underscoring the need for comprehensive genetic evaluation.
Area of Science:
- Oncology
- Genetics
- Clinical Diagnostics
Background:
- Tumor genomic profiling (TGP) sometimes incidentally detects germline pathogenic variants (PVs) linked to hereditary cancer syndromes.
- Somatic testing labs use different methods than germline labs for identifying germline PVs.
- Discrepancies between these testing methods can affect patient care.
Purpose of the Study:
- To evaluate discrepancies between somatic and germline genetic testing results.
- To assess the impact of these discrepancies on patient management and treatment decisions.
Main Methods:
- Retrospective chart review of patients undergoing both somatic and germline genetic testing at a single institution.
- Analysis of cases with discrepant results, including missed PVs and differing variant classifications.
Main Results:
- Of 600 patients with both tests, 109 had germline PVs identified.
- 20 cases showed discrepancies: 14 PVs missed by somatic testing, 6 with different classifications.
- 3 PVs identified by germline testing were targets for PARP inhibitors, altering treatment.
Conclusions:
- Somatic testing methods may not be optimized for germline PV detection, potentially missing critical findings.
- Unrecognized germline PVs can lead to missed hereditary syndrome diagnoses and lost targeted therapy opportunities.
- Comprehensive germline assessment is crucial for all patients meeting genetic evaluation criteria, irrespective of somatic testing results.
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