The discovery of cancer-predisposing syndromes (CPSs) using next-generation sequencing (NGS) technologies is of increasing importance in pediatric oncology with regard to diagnosis, treatment, surveillance, family counselling and research. Recent studies indicate that a considerable percentage of childhood cancers are associated with CPSs. However, the ratio of CPSs that are caused by inherited vs. de novo mutations (DNMs), the risk of recurrence, and even the total number of genes, which should be considered as a true cancer-predisposing gene, are still unknown. In contrast to sequencing only single index patients, family-based NGS of the germline is a very powerful tool for providing unique insights into inheritance patterns (e.g., DNMs, parental mosaicism) and types of aberrations (e.g., SNV, CNV, indels, SV). Furthermore, functional perturbations of key cancer pathways (e.g., TP53, FA/BRCA) by at least two co-inherited heterozygous digenic mutations from each parent and currently unrecognized rare variants and unmeasured genetic interactions between common and rare variants may be a widespread genetic phenomenon in the germline of affected children. Therefore, family-based trio sequencing has the potential to reveal a striking new landscape of inheritance in childhood cancer and to facilitate the integration and efforts of individualized treatment strategies, including personalized and preventive medicine and cancer surveillance programs. Consequently, cancer genetics is becoming an increasingly common approach in modern oncology, so trio-sequencing should also be routinely integrated into pediatric oncology.

中文翻译：

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癌症儿童的基于家庭的种系测序。

在诊断，治疗，监测，家庭咨询和研究方面，使用下一代测序（NGS）技术发现易患癌症的综合征（CPS）在儿科肿瘤学中越来越重要。最近的研究表明，相当多的儿童期癌症与CPS相关。然而，尚不清楚由遗传突变与新生突变（DNM）引起的CPS比例，复发风险，甚至基因总数，这些基因应被视为真正的癌症易感基因。与仅对单指标患者进行测序相比，基于种系的NGS是一种非常强大的工具，可为您提供有关遗传模式（例如DNM，父母亲镶嵌性）和畸变类型（例如SNV，CNV，插入缺失，SV）的独特见解）。此外，来自每个亲本的至少两个共同遗传的杂合双基因突变和目前无法识别的稀有变体以及常见和稀有变体之间无法测量的遗传相互作用可能是关键癌症途径（例如TP53，FA / BRCA）的功能性干扰患病儿童的种系。因此，基于家庭的三重测序有可能揭示儿童癌症遗传的新格局，并促进个性化治疗策略的整合和努力，包括个性化和预防性医学以及癌症监测计划。因此，癌症遗传学已成为现代肿瘤学中越来越普遍的方法，因此三重测序也应常规地纳入儿科肿瘤学。FA / BRCA）至少来自每个亲本的两个遗传的杂合双基因突变，以及目前无法识别的稀有变体以及常见和稀有变体之间无法测量的遗传相互作用，可能是受影响儿童种系中普遍存在的遗传现象。因此，基于家庭的三重测序有可能揭示儿童癌症遗传的新格局，并促进个性化治疗策略的整合和努力，包括个性化和预防性医学以及癌症监测计划。因此，癌症遗传学已成为现代肿瘤学中越来越普遍的方法，因此三重测序也应常规地纳入儿科肿瘤学。FA / BRCA）至少是由每个亲本共同遗传的两个杂合双基因突变，以及目前无法识别的稀有变体以及常见和稀有变体之间无法测量的遗传相互作用，这可能是受影响儿童种系中普遍存在的遗传现象。因此，基于家庭的三重测序有可能揭示儿童癌症遗传的新格局，并促进个性化治疗策略的整合和努力，包括个性化和预防性医学以及癌症监测计划。因此，癌症遗传学已成为现代肿瘤学中越来越普遍的方法，因此三重测序也应常规地纳入儿科肿瘤学。