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.

中文翻译：

---

频率和肉瘤中胚系致病性变异的临床特征：一项病例对照研究

背景 肉瘤患者尚未将全基因组多基因检测（MGPT）纳入标准护理。本研究旨在评估肉瘤患者与无癌对照组中胚系致病性变异（gPVs）的频率和分布，并确定有 gPVs 和无 gPVs 患者的差异。方法 这项回顾性队列包括 488 名肉瘤患者，以及按年龄、性别和种族 1:5 匹配的 2,440 名无癌对照组。MGPT 在 2016 年至 2024 年间在一个单一的胚系检测实验室进行。使用 Fisher 精确检验比较选定基因中 gPVs 的频率，并计算优势比（ORs）和 95%置信区间（CIs）。此外，在仅病例队列中，评估临床特征以评估与任何基因中 gPVs 存在的相关性。结果 在 488 名肉瘤患者中，67.8%（n = 331）为女性，肉瘤诊断的中位年龄为 47 岁（范围 0.5-87.5）。病例组中 gPVs 的频率高于对照组（26.2% vs. 10.5%；OR 3.05，p < .001）。我们观察到，与对照相比，在肉瘤患者中，gPVs在TP53、BRCA2、CHEK2、NF1、SDHA、BRIP1、POT1、RB1和CDH1基因中的频率更高。肉瘤诊断时的年龄在两组之间没有差异。结论：这项研究证实了在肉瘤患者中gPVs的高检出率，并描述了几个相关基因。这些发现表明，肉瘤诊断时的年龄可能无法可靠地预测gPVs。扩大肉瘤患者的基因检测将有助于个性化治疗策略和家庭风险评估。