文章：

发育起源塑造儿科癌症基因组

Developmental origins shape the paediatric cancer genome

原文发布日期：2024-05-02

DOI: 10.1038/s41568-024-00684-9

类型: Review Article

开放获取: 否

英文摘要：

In the past two decades, technological advances have brought unprecedented insights into the paediatric cancer genome revealing characteristics distinct from those of adult cancer. Originating from developing tissues, paediatric cancers generally have low mutation burden and are driven by variants that disrupt the transcriptional activity, chromatin state, non-coding cis-regulatory regions and other biological functions. Within each tumour, there are multiple populations of cells with varying states, and the lineages of some can be tracked to their fetal origins. Genome-wide genetic screening has identified vulnerabilities associated with both the cell of origin and transcription deregulation in paediatric cancer, which have become a valuable resource for designing new therapeutic approaches including those for small molecules, immunotherapy and targeted protein degradation. In this Review, we present recent findings on these facets of paediatric cancer from a pan-cancer perspective and provide an outlook on future investigations.

摘要翻译： 

在过去的二十年里，技术进步为儿科癌症基因组带来了前所未有的洞察，揭示出与成人癌症不同的特征。儿科癌症源于发育中的组织，通常具有较低的突变负荷，其驱动因素主要是破坏转录活性、染色质状态、非编码顺式调控区域和其他生物学功能的变异。每个肿瘤内部存在多种具有不同状态的细胞群体，其中一些细胞的谱系可追溯至胎儿起源。全基因组遗传筛选已识别出与儿科癌症起源细胞和转录失调相关的脆弱性，这些发现已成为设计新治疗方法（包括小分子药物、免疫疗法和靶向蛋白降解策略）的宝贵资源。本综述从泛癌种视角介绍儿科癌症这些方面的最新研究进展，并对未来研究方向提出展望。

原文链接：

Developmental origins shape the paediatric cancer genome