分离的DNA病变表明,瘤发起细胞具有较高的选择性优势
Vladimir Seplyarskiy1,2,3,4, Maha Shady1,2,5,6, Maria A Andrianova7
1Department of Biomedical Informatics, Harvard Medical School, Boston, MA, USA.
bioRxiv : the preprint server for biology
|November 19, 2025
概括
通过通过细胞分裂追踪DNA病变,更好地了解癌症的开始. 克隆通常很早就开始,在4个细胞代内,这表明癌症驱动因素的早期健康优势显著.
科学领域:
- 在瘤学瘤学.
- 遗传学 遗传学 是一个
- 细胞生物学 细胞生物学
背景情况:
- 识别产生癌症的细胞和跟踪早期分裂是一个挑战.
- 变异原体的DNA病变可以在细胞复制过程中持续存在.
- 这些病变的分离提供了癌症开始的足迹.
研究的目的:
- 在各种癌症环境中分析DNA损伤分离足迹.
- 估计DNA病变和瘤共同祖先之间的细胞分裂数量.
- 从早期事件中推断癌症发病和生长参数.
主要方法:
- 在小鼠模型,人类转移性瘤和患者血液中分析病变分离足迹.
- 应用一个分支过程模型来估计健身优势.
- 单细胞数据的家族遗传学分析.
主要成果:
- 克隆启动通常在研究系统中发生在4个细胞代内.
- 早期癌症的司机表现出超过30%的健身优势.
- 每个早期的细胞分裂至少会产生1.3个自我更新的细胞.
结论:
- DNA损伤分离为研究早期癌症发展提供了强大的方法.
- 瘤启动和生长动态可以从共同祖先前的事件中推断出来.
- 这种方法为癌症的起源和对治疗的反应提供了新的见解.
相关概念视频
Cancer Stem Cells and Tumor Maintenance
5.8K
Early diagnosis and treatment can often cure cancer. However, even with treatment, residual cells called cancer stem cells (CSC) might remain, often causing tumor recurrence. These cancer stem cells possess the potential for self-renewal and multi-lineage differentiation and are often responsible for the therapeutic resistance displayed in most cancers.
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
Cancer stem cells are thought to originate from tissue-specific normal stem cells or progenitor cells. The normal stem cells usually reside in...
5.8K
Adaptive Mechanisms in Cancer Cells
6.9K
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,...
Some of the advantages that cancer cells have on normal cells include - enhanced ability to divide without terminally differentiating, induce new blood vessel formation,...
6.9K
Loss of Tumor Suppressor Gene Functions
5.8K
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.
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
When the tumor suppressor genes develop mutations or are lost, cells start growing out of control, leading to cancer. However, a single functional copy of the tumor suppressor gene is enough for the cells to maintain their normal functions and cell...
5.8K
Cancers Originate from Somatic Mutations in a Single Cell
14.5K
Cancer arises from mutations in the critical genes that allow healthy cells to escape cell cycle regulation and acquire the ability to proliferate indefinitely. Though originating from a single mutation event in one of the originator cells, cancer progresses when the mutant cell lines continue to gain more and more mutations, and finally, become malignant. For example, chronic myelogenous leukemia (CML) develops initially as a non-lethal increase in white blood cells, which progressively...
14.5K
Cancer-Critical Genes II: Tumor Suppressor Genes
9.3K
Genes usually encode proteins necessary for the proper functioning of a healthy cell. Mutations can often cause changes to the gene expression pattern, thereby altering the phenotype.
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
When the function of certain critical genes, especially those involved in cell cycle regulation and cell growth signaling cascades, gets disrupted, it upsets the cell cycle progression. Such cells with unchecked cell cycles start proliferating uncontrollably and eventually develop into tumors.
Such genes that act...
9.3K
Targeted Cancer Therapies
8.6K
The targeted cancer therapies, also known as “molecular targeted therapies,” take advantage of the molecular and genetic differences between the cancer cells and the normal cells. It needs a thorough understanding of the cancer cells to develop drugs that can target specific molecular aspects that drive the growth, progression, and spread of cancer cells without affecting the growth and survival of other normal cells in the body.
There are several types of targeted therapies against...
There are several types of targeted therapies against...
8.6K


