在癌症的进化血统中量化细胞分裂
Martin Blohmer1,2,3, David M Cheek1,2, Wei-Ting Hung2,4
1Department of Genetics, Harvard Medical School, Boston, MA, USA.
Nature genetics
|February 5, 2025
概括
我们开发了一种简单的方法,使用DNA复制突变来计算细胞分裂. 这揭示了癌症的演变,显示更多的分裂与转移相关,结直肠和肺癌的存活率较低.
科学领域:
- 癌症生物学 癌症生物学
- 遗传学 是一个遗传学.
- 进化生物学 进化生物学
背景情况:
- 细胞分裂对体质进化和癌症进展至关重要.
- 在人类癌症中量化细胞分裂一直是一个重大挑战.
- 了解细胞分裂史对于癌症研究至关重要.
研究的目的:
- 开发和验证一种用于量化癌症细胞分裂的新型框架.
- 为了研究细胞分裂史和癌症进化里程碑之间的关系.
- 探索细胞分裂负担,转移能力和患者存活率之间的联系.
主要方法:
- 通过分析聚氨酸同聚合物中的DNA复制相关突变来计算细胞分裂的框架.
- 应用框架分析了来自37名结肠直肠癌患者的505个样本.
- 分析了73个多焦点肺癌样本的队列.
主要成果:
- 大肠直肠癌的原发性瘤在约250个细胞分裂时多样化,而远端转移在约500个分裂时分离.
- 远程转移,与淋巴结转移不同,起源于余分裂的原发性瘤区域,将扩散与转移潜力联系起来.
- 在肺癌中,共同祖先的细胞分裂负担区分了独立的原发性瘤与转移,与患者的存活率相关.
结论:
- 开发的框架提供了一种可访问的方法来确定癌症细胞分裂史.
- 细胞分裂史包含有价值的生物和临床信息,特别是在转移能力和患者预后方面.
- 广泛的扩散是结直肠和肺癌中转移潜力的关键因素.
更多相关视频
11:47Time-lapse Imaging of Primary Preneoplastic Mammary Epithelial Cells Derived from Genetically Engineered Mouse Models of Breast Cancer
Published on: February 8, 2013
11.8K
10:20Simultaneous Assessment of Kinship, Division Number, and Phenotype via Flow Cytometry for Hematopoietic Stem and Progenitor Cells
Published on: March 24, 2023
1.3K
相关概念视频
What is Cancer?
10.5K
Cells and tissues must meticulously coordinate their activities for the normal functioning of the human body. Therefore, they exhibit socially responsible behavior - resting, growing, dividing, differentiating, or dying - for the organism’s benefit. Cancer arises when cells divide uncontrollably and invade other tissues or organs.
Although people have known about cancer for centuries, it was only in 1761 that Giovanni Morgagni of Padua performed a detailed autopsy of...
Although people have known about cancer for centuries, it was only in 1761 that Giovanni Morgagni of Padua performed a detailed autopsy of...
10.5K
Cancers Originate from Somatic Mutations in a Single Cell
11.5K
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...
11.5K
Tumor Progression
6.2K
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...
6.2K
What is the Cell Cycle?
6.3K
The cell cycle refers to the sequence of events occurring throughout a typical cell’s life. In eukaryotic cells, the somatic cell cycle has two stages: the interphase and the mitotic phase. During interphase, the cell grows, performs its basic metabolic functions, copies its DNA, and prepares for mitotic cell division. Then, during mitosis and cytokinesis, the cell divides its nuclear and cytoplasmic materials, respectively. This generates two daughter cells that are identical to the...
6.3K
Cell Lines
7.2K
A cell line is a population of cells grown in vitro that can be subcultured over several generations. Normal cells cease to divide after a certain number of cell divisions, a process known as replicative senescence. This number, called the Hayflick limit, was conceptualized by Leonard Hayflick in 1961 when he observed that fetal cells grown in culture could only divide 40-60 times. This limit is due to the shortening of the telomeres during each round of cell division, preventing cell division...
7.2K
Replicative Cell Senescence
3.6K
Replicative cell senescence is a property of cells that allows them to divide a finite number of times throughout the organism's lifespan while preventing excessive proliferation. Replicative senescence is associated with the gradual loss of the telomere — short, repetitive DNA sequences found at the end of the chromosomes. Telomeres are bound by a group of proteins to form a protective cap on the ends of chromosomes. Embryonic stem cells express telomerase — an enzyme that adds...
3.6K
