在儿童癌症的患者衍生的异种移植模型中,异种染色体DNA的保存和克隆行为
bioRxiv : the preprint server for biology
|September 2, 2025
概括
超染色体DNA (ecDNA) 是儿童癌症的驱动因素. 来自患者的异种移植模型揭示了ecDNA在瘤进化中的作用,显示了其持久性和扩张,突出显示了其致癌潜力.
科学领域:
- 癌症学
- 遗传学
- 癌症生物学
背景情况:
- 染色体外DNA (ecDNA) 是癌症发生的一个重要驱动因素,与儿童癌症的预后不佳有关.
- 在临床前模型中了解ecDNA的行为对于开发向疗法至关重要.
研究的目的:
- 在患者衍生异种移植 (PDX) 模型中比较ecDNA的患病率,序列保存和克隆动态,与匹配的原始瘤进行比较.
- 评估PDX模型在儿童癌症中研究ecDNA的实用性.
主要方法:
- 338个PDX样本的全基因组测序和127个不同类型的儿童癌症的匹配原发性瘤.
- 单细胞多基因分析以分析ecDNA阳性细胞的克隆动态.
主要成果:
- 在患者瘤中发现的PDX模型经常重复瘤基因放大 (例如,MYCN,MYC,MDM2),具有很高的ecDNA序列保存.
- 骨髓母细胞瘤和神经母细胞瘤的PDX显示出显著更高的ecDNA流行率,这表明在传播过程中具有强烈的选择性或de novo形成.
- 单细胞分析表明,eDNA阳性克隆在PDX中持续存在或显著扩大,这表明有选择性的生长优势.
结论:
- 在儿童癌症研究中,PDX模型是有价值的系统.
- 在儿童癌症中,ecDNA具有选择性增长优势,推动瘤的演变和进展.
相关概念视频
Mouse Models of Cancer Study
Mice have long served as models for studying human biology and pathology because of their phylogenetic and physiological similarity with humans. They are also easy to maintain and breed in the laboratory, and hence, many inbred strains are now available for research. Studies on mice have contributed immeasurably to our understanding of cancer biology.
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
The development of transgenic, knockout, and knock-in mice has led to an exponential increase in their use as model organisms in research,...
Bone Marrow Sampling and Transplants
Bone marrow transplant is a potential cure for several diseases, including cancer and specific genetic disorders. Notably, this procedure is applicable for patients suffering from aplastic anemia, certain types of leukemia, severe combined immunodeficiency disease (SCID), Hodgkin's disease, non-Hodgkin's lymphoma, multiple myeloma, thalassemia, sickle-cell disease, and certain cancers.
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy the...
The transplant begins with high doses of chemotherapy and radiation treatment, which aim to destroy the...


