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Germline Genetic Testing in Patients with Bone and Soft Tissue Sarcoma: A Prospective Multicenter Study to Evaluate
Isaak Ailts1,2, Michael A Golafshar3, Katie L Kunze3
1Division of Hematology and Medical Oncology, Department of Medicine, Mayo Clinic, Phoenix, AZ 85054, USA.
International Journal of Molecular Sciences
|April 17, 2025
Summary
Germline testing in sarcoma patients revealed pathogenic variants in 8.7%, often missed by current guidelines. This testing can identify therapeutic options and assess familial cancer risk for rare sarcomas.
Area of Science:
- Oncology
- Genetics
- Cancer Research
Background:
- Sarcomas are rare, heterogeneous mesenchymal tumors with diverse biology and outcomes.
- The inciting factors for most sarcomas remain unclear, complicating diagnosis and treatment.
Purpose of the Study:
- To determine the prevalence of pathogenic germline variants (PGVs) in patients diagnosed with sarcoma.
- To evaluate the potential impact of germline testing for identifying therapeutic options and familial risk in sarcoma patients.
Main Methods:
- Prospective, multi-site study involving germline sequencing of 115 sarcoma patients using an 84-gene next-generation sequencing panel.
- Analysis of pathogenic/likely pathogenic variants (PGVs) and variants of uncertain significance (VUS) in relation to disease stage and patient demographics.
Main Results:
- Pathogenic germline variants (PGVs) were identified in 8.7% (10/115) of sarcoma patients.
- High-to-moderate penetrance gene abnormalities (e.g., TP53, BRCA1, ATM) were found in 80% of patients with PGVs.
- A significant proportion (70%) of detected PGVs would not have been identified using current clinical guidelines.
Conclusions:
- Germline sequencing in sarcoma patients can detect clinically significant PGVs, including those missed by current guidelines.
- Identifying PGVs in sarcoma patients offers potential for targeted therapeutic strategies and crucial familial risk assessment.
- Germline testing is a valuable tool given the rarity of sarcomas and limited treatment options for advanced disease.
