As next-generation sequencing (NGS) has become more widely used, germline and rare genetic variations responsible for inherited illnesses, including cancer predisposition syndromes (CPSs) that account for up to 10% of childhood malignancies, have been found. The CPSs are a group of germline genetic disorders that have been identified as risk factors for pediatric cancer development. Excluding a few “classic” CPSs, there is no agreement regarding when and how to conduct germline genetic diagnostic studies in children with cancer due to the constant evolution of knowledge in NGS technologies. Various clinical screening tools have been suggested to aid in the identification of individuals who are at greater risk, using diverse strategies and with varied outcomes. We present here an overview of the primary clinical and molecular characteristics of various CPSs and summarize the existing clinical genomics data on the prevalence of CPSs in pediatric cancer patients. Additionally, we discuss several ethical issues, challenges, limitations, cost-effectiveness, and integration of genomic newborn screening for CPSs into a healthcare system. Furthermore, we assess the effectiveness of commonly utilized decision-support tools in identifying patients who may benefit from genetic counseling and/or direct genetic testing. This investigation highlights a tailored and systematic approach utilizing medical newborn screening tools such as the genome sequencing of high-risk newborns for CPSs, which could be a practical and cost-effective strategy in pediatric cancer care.
随着下一代测序技术的广泛应用，已发现导致遗传性疾病的种系及罕见基因变异，其中包括占儿童恶性肿瘤高达10%的癌症易感综合征。癌症易感综合征是一组已被确认为儿童癌症发生风险因素的种系遗传性疾病。除少数"经典"综合征外，由于测序技术知识的持续更新，目前对于何时及如何对癌症患儿进行种系遗传诊断研究尚未形成共识。学界已提出多种临床筛查工具，通过不同策略帮助识别高风险个体，但实施效果存在差异。本文系统综述了各类癌症易感综合征的主要临床与分子特征，总结了当前关于儿童癌症患者中该综合征患病率的临床基因组学数据。同时探讨了将癌症易感综合征基因组新生儿筛查纳入医疗体系所涉及的伦理问题、实施挑战、技术局限性与成本效益。此外，评估了常用决策支持工具在识别需要遗传咨询和/或直接基因检测患者方面的有效性。本研究强调采用定制化系统方案，例如对高风险新生儿进行基因组测序等医疗筛查手段，这可能是儿科肿瘤诊疗中切实可行且具有成本效益的策略。
Genomic Newborn Screening for Pediatric Cancer Predisposition Syndromes: A Holistic Approach
肿瘤(癌症)患者之家