Foss-Skiftesvik Jon, Stoltze Ulrik Kristoffer
Department of Neurosurgery, Rigshospitalet University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.
The Pediatric Oncology Research Laboratory, Department of Pediatrics and Adolescent Medicine, Rigshospitalet University Hospital, Blegdamsvej 9, 2100, Copenhagen, Denmark.
Acta Neurochir (Wien). 2022 Nov;164(11):3025-3034. doi: 10.1007/s00701-022-05258-y. Epub 2022 Jun 3.
Historically, few pediatric central nervous system (CNS) tumors were thought to result from genetic predisposition. However, within the last decade, new DNA sequencing methods have led to an increased recognition of high-risk cancer predisposition syndromes in children with CNS tumors. Thus, genetic predisposition is increasingly impacting clinical pediatric neuro-oncology.
In this narrative review, we discuss the current understanding of genetic predisposition to childhood CNS tumors and provide a general overview of involved research methodologies and terminology. Moreover, we consider how germline genetics may influence neurosurgical practice.
Introduction of next-generation DNA sequencing has greatly increased our understanding of genetic predisposition to pediatric CNS tumors by enabling whole-exome/-genome sequencing of large cohorts. To date, the scientific literature has reported germline sequencing findings for more than 2000 children with CNS tumors. Although varying between tumor types, at least 10% of childhood CNS tumors can currently be explained by rare pathogenic germline variants in known cancer-related genes. Novel methodologies continue to uncover new mechanisms, suggesting that a much higher proportion of children with CNS tumors have underlying genetic causes. Understanding how genetic predisposition influences tumor biology and the clinical course in a given patient may mandate adjustments to neurosurgical treatment.
Germline genetics is becoming increasingly important to clinicians, including neurosurgeons. This review provides an updated overview of genetic predisposition to childhood CNS tumors with focus on aspects relevant to pediatric neurosurgeons.
从历史上看，很少有人认为小儿中枢神经系统（CNS）肿瘤是由遗传易感性引起的。然而，在过去十年中，新的DNA测序方法使人们越来越认识到患有中枢神经系统肿瘤的儿童存在高风险癌症易感综合征。因此，遗传易感性对临床小儿神经肿瘤学的影响越来越大。
在这篇叙述性综述中，我们讨论了目前对儿童中枢神经系统肿瘤遗传易感性的理解，并概述了相关的研究方法和术语。此外，我们考虑了种系遗传学如何影响神经外科实践。
下一代DNA测序的引入通过对大量队列进行全外显子组/基因组测序，极大地增加了我们对小儿中枢神经系统肿瘤遗传易感性的理解。迄今为止，科学文献已经报道了2000多名患有中枢神经系统肿瘤儿童的种系测序结果。虽然不同肿瘤类型有所差异，但目前已知癌症相关基因中罕见的致病性种系变异可解释至少10%的儿童中枢神经系统肿瘤。新的方法不断揭示新的机制，这表明有更高比例的中枢神经系统肿瘤儿童存在潜在的遗传原因。了解遗传易感性如何影响特定患者的肿瘤生物学和临床病程可能需要对神经外科治疗进行调整。
种系遗传学对包括神经外科医生在内的临床医生越来越重要。本综述提供了儿童中枢神经系统肿瘤遗传易感性的最新概述，重点关注与小儿神经外科医生相关的方面。
