Developments over the past five years have significantly advanced our ability to use genome-scale analyses-including high-density genotyping, transcriptome sequencing, exome sequencing, and genome sequencing-to identify the genetic basis of childhood cancer. This article reviews several key results from an expanding number of genomic studies of pediatric cancer: (a) Histopathologic subtypes of cancers can be associated with a high incidence of germline predisposition, (b) neurodevelopmental disorders or highly penetrant cancer predisposition syndromes can result from specific patterns of variation in genes encoding the SMARC family of chromatin remodelers, (c) genome-wide association studies with relatively small pediatric cancer cohorts have successfully identified single-nucleotide polymorphisms with large effect sizes and provided insight into population differences in cancer risk, and (d) multiple exome or genome analyses of unselected childhood cancer cohorts have yielded a 7-10% incidence of pathogenic variants in cancer predisposition genes. This work supports the increasing use of genomic sequencing in the care of pediatric cancer patients and at-risk family members.

中文翻译：

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基因组时代儿童癌症的遗传易感性。

过去五年的发展大大提高了我们使用基因组规模分析（包括高密度基因分型，转录组测序，外显子组测序和基因组测序）来鉴定儿童癌症的遗传基础的能力。本文回顾了越来越多的儿科癌症基因组研究得出的几个关键结果：（a）癌症的组织病理学亚型可能与种系易感性的高发生率相关；（b）神经发育障碍或高度渗透性的癌症易感性综合征可能是由于特定原因导致的编码SMARC染色质重塑剂家族的基因的变异模式，（c）与相对较小的儿科癌症队列相关的全基因组关联研究已成功鉴定出具有较大影响大小的单核苷酸多态性，并提供了对癌症风险人群差异的洞察力；以及（d）对未选出的儿童期癌症队列进行了多个外显子组或基因组分析在癌症易感基因中产生7-10％的致病变异。这项工作支持在儿科癌症患者和高危家庭成员的护理中越来越多地使用基因组测序。