相关实验视频

Updated: Jul 10, 2025

Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment

Visualization, Quantification, and Mapping of Immune Cell Populations in the Tumor Microenvironment

Published on: March 25, 2020

建模空间结构对实体瘤进化和ctDNA组成的影响

Thomas Rachman^1,2, David Bartlett³, William Laframboise³

¹Computational Biology Department, School of Computer Science, Carnegie Mellon University, Pittsburgh, PA, USA.

bioRxiv : the preprint server for biology

|November 21, 2023

概括

瘤中的空间变量细胞死亡可以扭曲循环瘤DNA (ctDNA) 档案,可能误导癌症的进化和治疗反应. 液体活检中的这种偏见可能导致不准确的临床决定.

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) 对于实时癌症监测,诊断和预后至关重要.
目前的ctDNA分析主要依赖于来自亡细胞或亡细胞的DNA.
固体瘤由于化疗和免疫透而表现出空间异质的细胞死亡率.

研究的目的:

研究空间变量细胞死亡如何影响驱动器突变积累和ctDNA表示.
模拟边缘偏差细胞死亡对瘤克隆代表性和ctDNA中突变检测能力的影响.
了解空间流失模式如何影响液体活检反映瘤状态的准确性.

主要方法:

利用了边界驱动瘤生长的随机进化模型.
模拟条件与瘤周边的细胞死亡率升高.
分析了空间分离偏差对ctDNA中的克隆组成,多样性和变异性等位基因频率 (VAF) 的影响.

主要成果:

侵入性克隆可以在ctDNA中因空间脱落偏差而过度代表.
克隆多样性可能在血液样本中出现人工升高.
亚克隆VAF可以被膨胀,静止瘤表现出类似的偏差,但检测能力降低.
检测极限显著影响空间偏差的感知.

结论:

空间结构化的细胞死亡可以导致液体活检中高度偏差的ctDNA档案.
偏差ctDNA档案可以提高扩张克隆的检测,但有可能准亚克隆变异.
了解空间变量细胞死亡对于准确解释液体活检数据和临床决策至关重要.

关键词:

ctDNActDNA是什么意思空间进化的空间演变.瘤DNA的流失是瘤DNA的流失.瘤的演变瘤的演变瘤生长模型瘤生长模型

更多相关视频

Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment

Micromanipulation of Circulating Tumor Cells for Downstream Molecular Analysis and Metastatic Potential Assessment

Published on: May 14, 2019

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma

Digital Spatial Profiling for Characterization of the Microenvironment in Adult-Type Diffusely Infiltrating Glioma

Published on: September 13, 2022

相关概念视频

The Tumor Microenvironment

The Tumor Microenvironment

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

Adaptive Mechanisms in Cancer Cells

Adaptive Mechanisms in Cancer Cells

Cancer cells accumulate genetic changes at an abnormally rapid rate due to the defects in the DNA repair mechanisms. From an evolutionary perspective, such genetic instability is advantageous for cancer development. Mutant cell lines accumulate a series of beneficial mutations that contribute to their progression into cancer.
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...