Assessment of cancer predisposition syndromes (CPS) in childhood tumours is challenging to paediatric oncologists due to inconsistent recognizable clinical phenotypes and family histories, especially in cohorts with unknown prevalence of germline mutations. Screening checklists were developed to facilitate CPS detection in paediatric patients; however, their clinical value have yet been validated. Our study aims to assess the utility of clinical screening checklists validated by genetic sequencing in an Asian cohort of childhood tumours. We evaluated 102 patients under age 18 years recruited over a period of 31 months. Patient records were reviewed against two published checklists and germline mutations in 100 cancer-associated genes were profiled through a combination of whole-exome sequencing and multiplex ligation-dependent probe amplification on blood-derived genomic DNA. Pathogenic germline mutations were identified in ten (10%) patients across six known cancer predisposition genes: TP53, DICER1, NF1, FH, SDHD and VHL. Fifty-four (53%) patients screened positive on both checklists, including all ten pathogenic germline carriers. TP53 was most frequently mutated, affecting five children with adrenocortical carcinoma, sarcomas and diffuse astrocytoma. Disparity in prevalence of germline mutations across tumour types suggested variable genetic susceptibility and implied potential contribution of novel susceptibility genes. Only five (50%) children with pathogenic germline mutations had a family history of cancer. We conclude that CPS screening checklists are adequately sensitive to detect at-risk children and are relevant for clinical application. In addition, our study showed that 10% of Asian paediatric solid tumours have a heritable component, consistent with other populations.

由于可识别的临床表型和家族史不一致，特别是在种系突变患病率未知的人群中，儿童肿瘤学家对癌症易感综合征（CPS）的评估对儿童肿瘤学家来说是一个挑战。制定了检查清单以促进儿科患者的CPS检测。但是，它们的临床价值尚未得到证实。我们的研究旨在评估在亚洲儿童期队列中通过基因测序验证的临床筛查清单的实用性。我们评估了在31个月内招募的102名18岁以下的患者。通过两个已发布的检查表对患者记录进行了审查，并通过全外显子测序和血液来源的基因组DNA的多重连接依赖性探针扩增相结合，对100个与癌症相关的基因的种系突变进行了分析。在六个已知的癌症易感基因中的十名（10％）患者中鉴定出致病性种系突变：TP53，DICER1，NF1，FH，SDHD和VHL。五十四名患者（53％）在两个检查表中均筛选出阳性，包括所有十种病原体种系携带者。TP53是最常见的突变，影响了五名患有肾上腺皮质癌，肉瘤和弥漫性星形细胞瘤的儿童。跨肿瘤类型的种系突变患病率的差异表明遗传易感性可变，并且暗示了新的易感性基因的潜在贡献。只有五名（50％）具有致病性生殖系突变的儿童有癌症家族史。我们得出的结论是，CPS筛查清单对检测高危儿童具有足够的敏感性，并且与临床应用有关。此外，我们的研究表明，亚洲小儿实体瘤中有10％具有可遗传的成分，与其他人群一致。