利用液体活检揭示RAS-MEK通路体质致病变体在额外头骨动脉静脉形形中
Kartik D Bhatia1,2, Dianne Sylvester3, Bhavna Padhye4,3,5
1The Children's Hospital at Westmead Clinical School, Faculty of Medicine and Health, The University of Sydney, Westmead, NSW, Australia. kartik.bhatia@sydney.edu.au.
Communications medicine
|December 5, 2025
概括
液体活检成功地确定了儿科动脉静脉变异 (AVM) 的遗传变异,支持RAS-MEK通路的参与. 这种微创手术技术为AVM分子表征提供了比传统活检更安全的替代方案.
科学领域:
- 遗传学 是一个遗传学.
- 血管生物学 血管生物学
- 儿科瘤学 儿科瘤学
背景情况:
- 动脉静脉形 (AVM) 与RAS-MEK通路中的体质遗传变异有关.
- 研究这些变体对于像MEK抑制剂这样的向疗法至关重要.
- 用于分子分析的开放活检在AVM患者中具有显著的出血风险.
研究的目的:
- 评估液体活检在儿科外动脉动脉瘤中识别体质遗传变异的有用性.
- 探索RAS-MEK通路在AVM病理生理学中的作用.
- 在这个患者群体中评估液体活检的安全性和有效性.
主要方法:
- 液体活检样本从10名患有额外头骨AVM的儿童和年轻成年人的干静脉中收集.
- 通过下一代测序确定了体质变异.
- 分析了与采样位置和栓塞状态相关的变异性等位基因频率.
主要成果:
- 在十分之八的患者中检测到体质马赛克变体.
- 没有报告任何程序并发症.
- 鉴定出的变异包括KRAS,HRAS,其他RAS-MEK通路基因和PIK3CA.
- 五名患者在分子向药物治疗中表现出改善的结果.
- 变异性等位基因频率与靠近AVM基因的距离相关.
结论:
- 液体活检是一种有效和安全的基因定型方法,用于确定儿科外动脉动脉瘤的基因.
- RAS-MEK通路与AVM的发展有关.
- 在AVM中无细胞DNA碎片化模式提供了关于损伤内血动力学的见解.
相关概念视频
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
01:20The Retinoblastoma Gene
Tumor suppressor genes are normal genes that can slow down cell division, repair DNA mistakes, or program the cells for apoptosis in case of irreparable damage. Hence, they play an essential role in preventing the proliferation of damaged cells.
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...
The first-ever tumor suppressor gene called Rb was identified in retinoblastoma - a rare eye tumor in children. In inherited forms of the disease, a child inherits one defective copy of the Rb gene, which predisposes them to retinoblastoma. However,...