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循环的无细胞甲基化DNA揭示了来自辐射治疗的组织特异性细胞损伤

Megan E McNamara¹, Netanel Loyfer², Amber J Kiliti¹

¹Lombardi Comprehensive Cancer Center, Georgetown University Medical Center, Washington DC, USA.

|June 15, 2023

概括

这项研究引入了一种使用无细胞甲基化DNA检测健康组织辐射损伤的新方法. 这种技术提供了一种精确的方法来测量器官中的生物有效辐射剂量.

科学领域:

生物医学科学生物医学科学
分子生物学分子生物学
在瘤学瘤学.

背景情况:

放射治疗是癌症治疗的关键方法,但往往会对健康组织造成附带损伤.
在特定器官中评估这种损伤具有挑战性.
循环中的无细胞DNA (cfDNA) 是关于组织损伤的潜在信息来源.

研究的目的:

开发和验证一种方法,用无细胞甲基化DNA评估健康组织中辐射诱导的细胞损伤.
用DNA甲基化图谱将循环cfDNA片段映射到特定的人类和小鼠组织中.
评估辐射对各种器官的剂量依赖性和组织特异性影响.

主要方法:

建立了基于测序的,针对细胞类型的DNA甲基化图谱,用于绘制cfDNA的地图.
从血清样本中捕获cfDNA片段,使用混合化对CpG丰富的DNA面板进行混合.
将cfDNA片段映射到已建立的甲基化图谱中,以确定组织来源.
在小鼠模型和接受放射治疗的人类患者中分析了cfDNA.

主要成果:

细胞类型特定的DNA块在很大程度上被低甲基化,并且位于特征基因内.
在小鼠中,胸部辐射以剂量依赖的方式增加了血清中的肺内皮和心肌细胞甲基化DNA.
在乳腺癌患者中,放射治疗显示出明显的剂量依赖性和组织特异性的上皮和内皮反应.
右侧乳腺癌治疗在循环中增加了肝细胞和肝脏内皮DNA,表明肝脏的影响.

结论:

无细胞甲基化DNA的变化可以揭示细胞类型特定的辐射效应.
这种方法为健康组织中的生物有效辐射剂量提供了有价值的读数.
这些发现对监测和管理放射治疗副作用有意义.

关键词:

乳腺癌乳腺癌乳腺癌表观遗传学在表观遗传学中,表观遗传学是指表观遗传学.遗传学遗传学是一个在瘤学瘤学.放射治疗疗法放射治疗疗法

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