建模空间结构对固体瘤进化和循环瘤DNA组成的影响
Thomas Rachman1,2, David Bartlett3, William LaFramboise3
1Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA 15213, USA.
Cancers
|March 13, 2024
概括
瘤中的空间变量细胞死亡可以扭曲循环的瘤DNA (ctDNA) 档案. 这种ctDNA的偏差可能导致不准确的癌症评估和治疗决策,突出了未来研究的关键领域.
科学领域:
- 在瘤学瘤学.
- 基因组学就是基因组学.
- 计算生物学 计算生物学
背景情况:
- 循环瘤DNA (ctDNA) 监测对于实时瘤进化跟踪,诊断,治疗指导和预后至关重要.
- 目前的ctDNA分析主要依赖于来自亡或亡细胞的DNA,这些细胞可能受到瘤微环境因素的影响,如化疗和免疫透.
研究的目的:
- 研究瘤边界的空间可变细胞死亡率如何影响驱动突变积累和ctDNA表示.
- 模拟偏向细胞脱落对克隆组成,突变检测能力和ctDNA中变异性等位基因频率 (VAF) 的影响.
主要方法:
- 利用了边界驱动瘤生长的随机进化模型.
- 模拟的条件与瘤周边的细胞死亡率升高.
- 分析了对驱动器突变积累,克隆表征和ctDNA中VAFs的影响.
主要成果:
- 空间变化的细胞死亡可能导致ctDNA中侵入性克隆的过度代表.
- 观察到亚克隆VAF的潜在膨胀和血液样本中克隆多样性的明显升高.
- 证明具有空间脱落偏差的静止瘤较难检测,检测极限影响感知偏差.
结论:
- 空间结构化的细胞死亡可以显著偏差ctDNA配置文件,可能误解真正的瘤状态.
- 虽然有偏见的脱落可能会提高扩张克隆的检测,但它有可能引导治疗向亚克隆变异.
- 需要进一步的研究,以了解空间可变细胞死亡对ctDNA组成及其对癌症管理的影响的临床影响.
相关概念视频
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02:07Tumor Progression
Tumor progression is a phenomenon where the pre-formed tumor acquires successive mutations to become clinically more aggressive and malignant. In the 1950s, Foulds first described the stepwise progression of cancer cells through successive stages.
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...
Colon cancer is one of the best-documented examples of tumor progression. Early mutation in the APC gene in colon cells causes a small growth on the colon wall called a polyp. With time, this polyp grows into a benign, pre-cancerous tumor. Further...