文章：

重新设想儿童和青少年癌症的遗传易感性

Re-envisioning genetic predisposition to childhood and adolescent cancers

原文发布日期：2024-12-03

DOI: 10.1038/s41568-024-00775-7

类型: Review Article

开放获取: 否

英文摘要：

Although cancer is rare in children and adolescents, it remains a leading cause of death within this age range, and genetic predisposition is the main known risk factor. Since the discovery of retinoblastoma-predisposing RB1 pathogenic germline variants in 1985, several additional high-penetrance cancer predisposition genes (CPGs) have been identified. Although few clinically recognizable genetic conditions display moderate cancer phenotypes, burden testing has revealed low-to-moderate penetrance CPGs. In addition to germline pathogenic variants in CPGs, postzygotic somatic mosaic CPG pathogenic variants acquired during embryonic development are increasingly recognized as factors that predispose children and adolescents to malignancies. Genome-wide association studies of various childhood and adolescent cancer types have identified some common low-risk cancer susceptibility alleles. Although the clinical utility of polygenic risk scores is currently limited in children and adolescents, polygenic risk scores developed for adults can predict subsequent cancer risks in childhood and adolescent cancer survivors. In this Review, I describe our current knowledge of genetic predisposition to childhood and adolescent cancers. Survival rates in children and adolescents with cancer and CPGs are often poor, necessitating better integration of genomic testing into clinical care to improve cancer prevention, surveillance and therapies.

摘要翻译： 

尽管癌症在儿童和青少年中较为罕见，但仍是该年龄段的主要致死原因，而遗传易感性是已知的主要风险因素。自1985年发现视网膜母细胞瘤易感基因RB1的致病性胚系变异以来，已陆续鉴定出多个其他高外显率癌症易感基因（CPGs）。虽然具有中度癌症表型的临床可识别遗传病症较少，但负荷检测已揭示出中低外显率的CPGs。除CPGs的胚系致病性变异外，胚胎发育过程中获得的合子后体细胞嵌合型CPG致病性变异，日益被认为是儿童和青少年恶性肿瘤的易感因素。针对不同儿童及青少年癌症类型的全基因组关联研究，已识别出部分常见的低风险癌症易感等位基因。虽然多基因风险评分在儿童和青少年中的临床适用性目前有限，但针对成人开发的多基因风险评分可预测儿童及青少年癌症幸存者后续的癌症风险。本文综述了当前对儿童和青少年癌症遗传易感性的认知。携带CPGs的儿童和青少年癌症患者生存率通常较低，这需要将基因组检测更好地整合到临床护理中，以改进癌症预防、监测和治疗方法。

原文链接：

Re-envisioning genetic predisposition to childhood and adolescent cancers