UNASSIGNED: gWGS was performed in 309 children at diagnosis of CNS (n = 123, 40%) or extracranial (n = 186, 60%) solid tumors and analyzed for disease-causing variants in 189 known cancer predisposing genes. Tumor sequencing data were available for 74% (227/309) of patients. In addition, a standardized clinical assessment for underlying predisposition was performed in 95% (293/309) of patients.
UNASSIGNED: The prevalence of ChiCaP diagnoses was 11% (35/309), of which 69% (24/35) were unknown at inclusion (diagnostic yield 8%, 24/298). A second-hit and/or relevant mutational signature was observed in 19/21 (90%) tumors with informative data. ChiCaP diagnoses were more prevalent among patients with retinoblastomas (50%, 6/12) and high-grade astrocytomas (37%, 6/16), and in those with non-cancer related features (23%, 20/88), and ≥2 positive ChiCaP criteria (28%, 22/79). ChiCaP diagnoses were autosomal dominant in 80% (28/35) of patients, yet confirmed de novo in 64% (18/28). The 35 ChiCaP findings resulted in tailored surveillance (86%, 30/35) and treatment recommendations (31%, 11/35).
UNASSIGNED: Overall, our results demonstrate that systematic phenotyping, combined with genomics-based diagnostics of ChiCaP in children with solid tumors is feasible in large-scale clinical practice and critically guides personalized care in a sizable proportion of patients.
UNASSIGNED: The study was supported by the Swedish Childhood Cancer Fund and the Ministry of Health and Social Affairs.
■对309名诊断为中枢神经系统(n=123,40%)或颅外(n=186,60%)实体瘤的儿童进行了gWGS,并分析了189个已知的癌症易感基因中的致病变异。肿瘤测序数据可用于74%(227/309)的患者。此外,95%(293/309)的患者对潜在易感性进行了标准化临床评估.
■ChiCaP诊断的患病率为11%(35/309),其中69%(24/35)在纳入时未知(诊断率8%,24/298)。在具有信息数据的19/21(90%)肿瘤中观察到第二次命中和/或相关突变特征。ChiCaP诊断在视网膜母细胞瘤患者中更为普遍(50%,6/12)和高级星形细胞瘤(37%,6/16),在那些具有非癌症相关特征的人群中(23%,20/88),和≥2个阳性ChiCaP标准(28%,22/79).ChiCaP诊断为80%(28/35)的患者常染色体显性遗传,但仍在64%(18/28)中确认从头。35项ChiCaP调查结果导致了量身定制的监测(86%,30/35)和治疗建议(31%,11/35).
■总的来说,我们的结果表明,系统的表型,与基于基因组学的ChiCaP诊断相结合,在大规模临床实践中是可行的,并且在相当大比例的患者中指导个性化护理.
■这项研究得到了瑞典儿童癌症基金会和卫生与社会事务部的支持。