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Abstract：
Data on germline mutations in soft tissue and bone sarcomas are scarce. We sought to identify the prevalence of germline mutations in adult sarcoma patients treated at a tertiary cancer center. Newly diagnosed patients were offered germline genetic testing via an 84-gene panel. The prevalence of pathogenic germline variants (PGVs) and their association with disease-, and patient- related factors are reported. A total of 87 patients were enrolled, the median age was 48 (19-78) years, and 47 (54%) were females. Gastrointestinal stromal tumors (n = 12, 13.8%), liposarcoma (n = 10, 11.5%), and Ewing sarcoma (n = 10, 11.5%) were the main subtypes. A total of 20 PGVs were detected in 18 (20.7%) patients. Variants of uncertain significance, in the absence of PGVs, were detected in 40 (45.9%) patients. Young age (p = 0.031), presence of a second primary cancer (p = 0.019), and female gender (p = 0.042) were correlated with the presence of PGVs. All identified PGVs have potential clinical actionability and cascade testing, and eight (44.44%) suggested eligibility for a targeted therapy. Almost one in five adult patients with soft tissue and bone sarcomas harbor pathogenic or likely pathogenic variants. Many of these variants are potentially actionable, and almost all have implications on cancer screening and family counselling. In this cohort from the Middle East, younger age, presence of a second primary tumor, and female gender were significantly associated with higher PGVs rates. Larger studies able to correlate treatment outcomes with genetic variants are highly needed.
摘要：
关于软组织和骨肉瘤种系突变的数据很少。我们试图确定在三级癌症中心治疗的成年肉瘤患者中种系突变的患病率。通过84基因小组为新诊断的患者提供了种系基因检测。致病性种系变异（PGV）的患病率及其与疾病的关系，并报告患者相关因素。共纳入87例患者，中位年龄为48（19-78）岁，47名(54%)为女性。胃肠道间质瘤（n=12，13.8%），脂肪肉瘤（n=10，11.5%），尤因肉瘤(n=10，11.5%)是主要亚型。18例(20.7%)患者共检测到20例PGV。意义不确定的变体，在没有PGV的情况下，在40例（45.9％）患者中检测到。年轻的年龄（p=0.031），存在第二原发癌（p=0.019），女性（p=0.042）与PGV的存在相关。所有确定的PGV具有潜在的临床可操作性和级联测试，8人(44.44%)建议接受靶向治疗.几乎五分之一的软组织和骨肉瘤成年患者具有致病性或可能的致病性变异。这些变体中的许多都可能是可行的，几乎所有这些都对癌症筛查和家庭咨询有影响。在这个来自中东的群体中，年龄较小,第二个原发性肿瘤的存在，和女性性别与较高的PGV比率显着相关。非常需要能够将治疗结果与遗传变异相关联的更大规模的研究。
