文章：

儿童癌症治疗长期不良反应的遗传和表观遗传基础

Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy

原文发布日期：2024-11-07

DOI: 10.1038/s41568-024-00768-6

类型: Review Article

开放获取: 否

英文摘要：

Over the past decade, genome-scale molecular profiling of large childhood cancer survivorship cohorts has led to unprecedented advances in our understanding of the genetic and epigenetic bases of therapy-related adverse health outcomes in this vulnerable population. To facilitate the integration of knowledge generated from these studies into formulating next-generation precision care for survivors of childhood cancer, we summarize key findings of genetic and epigenetic association studies of long-term therapy-related adverse effects including subsequent neoplasms and cardiomyopathies among others. We also discuss therapy-related genotoxicities including clonal haematopoiesis and DNA methylation, which may underlie accelerated molecular ageing. Finally, we highlight enhanced risk prediction models for survivors of childhood cancer that incorporate both genetic factors and treatment exposures, aiming to achieve enhanced accuracy in predicting risks for this population. These new insights will hopefully inspire future studies that harness both expanding omics resources and evolving data science methodology to accelerate the translation of precision medicine for survivors of childhood cancer.

摘要翻译： 

在过去的十年中，对大规模儿童癌症幸存者队列进行的基因组尺度分子谱分析，使我们对这一脆弱群体治疗相关不良健康结局的遗传和表观遗传基础的理解取得了前所未有的进展。为了促进将这些研究产生的知识整合到制定下一代儿童癌症幸存者的精准护理中，我们总结了长期治疗相关不良反应（包括后续肿瘤和心肌病等）的遗传和表观遗传关联研究的关键发现。我们还讨论了治疗相关的基因毒性，包括克隆性造血和DNA甲基化，这些可能是加速分子老化的基础。最后，我们重点介绍了结合遗传因素和治疗暴露的儿童癌症幸存者增强风险预测模型，旨在提高预测该群体风险的准确性。这些新见解有望启发未来的研究，利用不断扩展的组学资源和不断发展的数据科学方法，加速儿童癌症幸存者精准医学的转化。

原文链接：

Genetic and epigenetic bases of long-term adverse effects of childhood cancer therapy