工程外染色体瘤基因放大促进瘤发生
Davide Pradella1, Minsi Zhang1,2, Rui Gao1,3
1Cancer Biology and Genetics Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Nature
|December 18, 2024
概括
科学家在细胞和小鼠中使用染色体外DNA (ecDNA) 进行了大型焦点基因放大. 这一突破使得研究癌症相关突变和开发新的临床前癌症模型成为可能.
科学领域:
- 分子生物学
- 遗传学
- 癌症研究
背景情况:
- 焦点基因放大是常见的癌症突变.
- 在模型系统中设计这些放大是困难的.
研究的目的:
- 使用染色体外DNA (ecDNA) 进行大型焦点基因放大工程的一般策略.
- 调查ecDNA中介放大在瘤发生中的作用.
- 为癌症研究创建新的临床前模型.
主要方法:
- 通过ecDNAs以时空控制的方式进行大焦放大.
- 配合 ecDNA 形成与可选择标记来跟踪 ecDNA 动态.
- 产生具有Cre诱导性Myc和Mdm2含有ecDNA的小鼠.
- 在小鼠模型中证明了ecDNA驱动的瘤形成.
主要成果:
- 在细胞和小鼠中使用ecDNA成功设计了大型焦点放大.
- 在初级细胞中观察到自发的ecDNA积累,促进增殖,不朽化和转化.
- 显示Mdm2含有的ecDNA在小鼠中促进肝细胞癌的形成.
结论:
- 开发的策略可以通过ecDNAs对大型焦点基因放大进行控制工程.
- 这种方法为ecDNA在瘤形成中的作用提供了洞察力.
- 该方法对研究ecDNA生物学和开发临床前癌症模型具有价值.
相关概念视频
Cancer-Critical Genes I: Proto-oncogenes
8.7K
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...
8.7K
Induced Pluripotent Stem Cells
3.9K
Stem cells are undifferentiated cells that divide and produce different cell types. Ordinarily, cells that have differentiated into a specific cell type are terminally differentiated; however, scientists have found a way to reprogram these mature cells so that they dedifferentiate and return to an unspecialized, proliferative state. These cells are pluripotent like embryonic stem cells—able to produce all cell types—and are called induced pluripotent stem cells (iPSCs).
Somatic...
Somatic...
3.9K
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
Mutagenicity and Carcinogenicity
1.2K
Mutagenicity and carcinogenicity refer to the ability of drugs to cause genetic defects and induce cancer, respectively. The International Agency for Research on Cancer (IARC) classifies agents into four groups based on their carcinogenic potential. Group 1 agents are known human carcinogens; group 2A agents are probably carcinogenic to humans; group 3 agents lack data to support their role in carcinogenesis; and group 4 includes agents for which data support that they are not likely to be...
1.2K
mTOR Signaling and Cancer Progression
3.7K
The mammalian target of rapamycin or mTOR protein was discovered in 1994 due to its direct interaction with rapamycin. The protein gets its name from a yeast homolog called TOR. The mTOR protein complex in mammalian cells plays a major role in balancing anabolic processes such as the synthesis of proteins, lipids, and nucleotides and catabolic processes, such as autophagy in response to environmental cues, such as availability of nutrients and growth factors.
The mTOR pathway or the...
The mTOR pathway or the...
3.7K
Adaptive Mechanisms in Cancer Cells
5.7K
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,...
5.7K


