据报道,几种癌症易感性综合征(CPS)易患横纹肌肉瘤,最常见于胚胎性横纹肌肉瘤儿童。对于CPS在肺泡横纹肌肉瘤(ARMS)患者中的作用存在挥之不去的疑问,通常由FOXO1融合癌蛋白驱动。我们进行了系统评价,以确定接受种系DNA测序的FOXO1融合阳性ARMS(FP-ARMS)患者。我们估计了癌症易感基因(CPG)和CPS中致病性/可能致病性(P/LP)变异的患病率。我们纳入了19篇出版物,报道了191例FP-ARMS患者。在26/191(13.6%)患者中发现了CPGs中的P/LP变异,其中9例(4.9%)与CPS诊断相关.CPS和FP-ARMS之间的因果关系的证据无法通过本综述的现有数据进行评估。只有一名患者患有已知易患横纹肌肉瘤的CPS,Li-Fraumeni综合征.典型的CPS与横纹肌肉瘤的关联很少见,但并非不存在,FP-ARMS患者。FOXO1融合状态,独自一人,不足以让临床医生依靠区分有/没有CPS的患者。
Several cancer predisposition syndromes (CPS) are reported to predispose to rhabdomyosarcoma, most frequently in children with embryonal rhabdomyosarcoma. There are lingering questions over the role of CPS in individuals with alveolar rhabdomyosarcoma (ARMS), which are frequently driven by FOXO1 fusion oncoproteins. We conducted a systematic
review to identify patients with FOXO1 fusion-positive ARMS (FP-ARMS) who underwent germline DNA sequencing. We estimated the prevalence of pathogenic/likely pathogenic (P/LP) variants in cancer predisposing genes (CPGs) and of CPSs. We included 19 publications reporting on 191 patients with FP-ARMS. P/LP variants in CPGs were identified in 26/191 (13.6%) patients, nine (4.9%) of which were associated with a CPS diagnosis. Evidence for causal associations between CPSs and FP-ARMS could not be assessed with available data from this
review. Only one patient was affected with a CPS known to predispose to rhabdomyosarcoma, Li-Fraumeni syndrome. Typical CPS associations with rhabdomyosarcoma are rare, but not nonexistent, in patients with FP-ARMS. FOXO1 fusion status, alone, is insufficient for clinicians to rely on to distinguish between patients with/without CPS.