What type of study is this?

This is a Case-Control Study study.

October 16, 2025

Frequency and clinical features of germline pathogenic variants in sarcoma: a case-control study

Puntos clave

Patients with sarcoma had a higher frequency of germline pathogenic variants compared to cancer-free controls, indicating genetic factors may influence sarcoma.
26.2% of sarcoma patients had germline pathogenic variants, in contrast to 10.5% in controls, with an odds ratio of 3.05.
The study evaluated clinical characteristics associated with germline pathogenic variants within a cohort of 488 sarcoma patients, highlighting the need for genetic testing.
Results suggest that current age at sarcoma diagnosis may not predict the presence of germline pathogenic variants, indicating a gap in personalized risk assessment.

Resumen

Abstract Background Germline multi-gene panel testing (MGPT) is not yet integrated into standard care for patients with sarcoma. This study aimed to assess the frequency and distribution of germline pathogenic variants (gPVs) in patients with sarcoma compared to cancer-free controls and identify differences between patients with and without gPVs. Methods This retrospective cohort included 488 sarcoma patients, and 2,440 cancer-free controls matched 1:5 by age, sex, and ethnicity. MGPT was performed between 2016 and 2024 at a single germline testing laboratory. The frequency of gPVs in selected genes was compared using Fisher’s exact test, with odds ratios (ORs) and 95% confidence intervals (CIs). Additionally, within the case-only cohort, clinical characteristics were evaluated to assess associations with the presence of gPVs in any gene. Results Among 488 patients with sarcoma, 67.8% (n = 331) were female, with a median age at sarcoma diagnosis of 47 years (range 0.5-87.5). Cases had a higher frequency of gPVs compared to controls (26.2% vs. 10.5%; OR 3.05, p .001). We observed a higher frequency of gPVs in TP53, BRCA2, CHEK2, NF1, SDHA, BRIP1, POT1, RB1, and CDH1 among patients with sarcoma compared to controls. Age at sarcoma diagnosis did not differ between groups. Conclusions This study confirms the high detection rate of gPVs in patients with sarcoma and describes several associated genes. These findings indicate that age at sarcoma diagnosis may not reliably predict gPVs. Expanding germline testing for patients with sarcoma would enhance personalized treatment strategies and familial risk assessment.

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